key: cord-0704961-zry01ji5
authors: Ali, Sofi Imtiyaz; Sheikh, Wajid Mohammad; Rather, Muzafar Ahmad; Venkatesalu, Venugopalan; Muzamil Bashir, Showkeen; Nabi, Showkat Ul
title: Medicinal plants: Treasure for antiviral drug discovery
date: 2021-02-16
journal: Phytother Res
DOI: 10.1002/ptr.7039
sha: 37a9b54629d134a4dcd800675699fb1892a6d11a
doc_id: 704961
cord_uid: zry01ji5

The pandemic of viral diseases like novel coronavirus (2019‐nCoV) prompted the scientific world to examine antiviral bioactive compounds rather than nucleic acid analogous, protease inhibitors, or other toxic synthetic molecules. The emerging viral infections significantly associated with 2019‐nCoV have challenged humanity's survival. Further, there is a constant emergence of new resistant viral strains that demand novel antiviral agents with fewer side effects and cell toxicity. Despite significant progress made in immunization and regenerative medicine, numerous viruses still lack prophylactic vaccines and specific antiviral treatments that are so often influenced by the generation of viral escape mutants. Of importance, medicinal herbs offer a wide variety of therapeutic antiviral chemotypes that can inhibit viral replication by preventing viral adsorption, adhering to cell receptors, inhibiting virus penetration in the host cell, and competing for pathways of activation of intracellular signals. The present review will comprehensively summarize the promising antiviral activities of medicinal plants and their bioactive molecules. Furthermore, it will elucidate their mechanism of action and possible implications in the treatment/prevention of viral diseases even when their mechanism of action is not fully understood, which could serve as the base for the future development of novel or complementary antiviral treatments.

. Viruses need to use host cell machines for several functions. Therefore, their obligatory parasitic nature and antiviral approaches must be applied directly to a virus to minimize interference with the host cell functions (Adalja & Inglesby, 2019) .

Further, the virus acts as barriers to broad-spectrum antiviral agents, including distinctions among RNA and DNA viruses, completely distinct virally encoded proteins, single or double genomic structure, cycles of cytoplasmic or nuclear replication, and degree of dependence on host proteins (Schoeman & Fielding, 2019) . The global antiviral drug armamentarium is expanding exponentially and is now covering many viral families. Nonetheless, very few known antiviral agents have activity spectrums that even marginally match up to the penicillin or sulfa range, the very first antibacterial agents identified.

The Earth's planet constitutes approximately 1,031 viruses, and their pervasiveness has colonized the marine ecosystem, where about 5,000 viral genomes seem to be prevalent in every 200 L of water (Breitbart & Rohwer, 2005) . Also, viruses continue moving between the environments. They are available worldwide, for example, in deep Ocean, polar ices, alkaline, hot, and salt waters, and are about 2,000 m deep in the terrestrial ecosystem. There have been nearly 20 families of viruses that certainly infect humans (Harvey, Champe, Fisher, & Strohl, 2006) , and many of them also trigger diseases in animals (Mahzounieh, Moghtadaei, & Zahraei Salehi, 2006) . Virus particles contact the living system, and if they inundate the human immune response, then preventing their expansion in the body would be almost unfeasible. For the sake of their frequent replication, they control the host biochemical pathway/metabolic processes and make their treatment almost tricky. However, it is now well comprehended that viruses are specific in their replication mode that could be effectively approached (Syed, Amako, & Siddiqui, 2010) . For instance, the proteolytic enzyme enhances viral maturation by distinguishing the viral polyprotein predecessor, whose obstruction would prevent its growth (Wapling, Srivastava, Shehu-Xhilaga, & Tachedjian, 2007) . The epidemic outbreaks caused by emerging and re-emerging viruses represent a critical threat to public health, mainly when preventive vaccines and antiviral therapies are unavailable. Several hard-to-cure diseases and complex syndromes, including Alzheimer's disease, type 1 diabetes, and hepatocellular carcinoma (HCC), have also been associated with viral infection (M. J. Ball, Lukiw, Kammerman, & Hill, 2013; Hober et al., 2012; Morgan et al., 2013) . However, many viruses remain without adequate immunization and, only a few antiviral drugs are licensed for clinical practice. The situation is further exacerbated by drug-resistant mutants' especially when using viral enzyme-specific inhibitors, which significantly hampers drug efficacy (Geretti, Armenia, & Ceccherini, 2012; Locarnini & Yuen, 2010) . Hence, there is an urgent need to discover novel antivirals that are highly productive and cost-effective for managing and controlling viral infections when vaccines and standard therapies lack.

New viral infections needed quite advanced drug molecules; however, the process of establishing such approaches toward this moment seems to have been sluggish and filled with impediments (Desselberg, 2000) . Antiviral chemotherapy has proceeded at a snaillike pace, unlike antibiotics that had attained a specific treatment level in three decades. Nevertheless, it ended up taking nearly 60 years for antiviral development to achieve its current prevalence position. The evolution of diagnosis for Hepatitis C is a prime illustration of how complicated the antiviral effect can be. However, cumulative and aimed antiviral therapy has proven to be an excellent strategy for treating viral infectious disease.

Viruses are amongst the substantial causes of mortality and morbidity globally (GBD 2017 Disease and Injury Incidence and Prevalence Collaborators, 2018; WHO, 2015) . Antiviral drugs and vaccines are being used to control human viral infections (De Clercq & Li, 2016) . Eventually, the main focus was on "one drug, one virus" dogma, which depends solely on targeting virus-specific factors. A counterstatement to this is "one drug multiple viruses" (BSAAs), as viruses utilize similar pathways and host factors to replicate within a cell (Bekerman & Einav, 2015; Bosl et al., 2019; de Clercq & Montgomery, 1983; De bing, Neyts, & Delang, 2015; Ianevski, Andersen, Merits, Bjoras, & Kainov, 2019; Rada & Dragun, 1977; Sidwell et al., 1972) . Though the concept of BSAAs was about 50 years ago, due to the recent outbreaks of a novel coronavirus (2019-nCoV) and several other viral infections, the field has acquired new urgency for the discovery of novel host-directed agents and the expansion of a drug repositioning methodology (Paraskevis et al., 2020) .

Drug repurposing, also known as repositioning, redirecting, reprofiling, is a strategic approach for accumulating additional benefits from an approved drug by approaching a disease apart from that it was initially envisioned (Nishimura & Hara, 2018; Pushpakom et al., 2019) . It has distinct advantages over new drug discovery since chemical synthesis, manufacturing processes, reliable safety, and pharmacokinetic properties are accessible in pre-clinical and early clinical development phases. Consequently, the repositioning of launched or perhaps failed viral drugs offer incredible translational opportunities, such as a substantially higher probability of commercial success in comparison to the implementation of novel virus-specific medicines and vaccines and a substantially decreased cost and timeframe for clinical accessibility Pizzorno, Padey, Terrier, & 

Viruses are organic artifacts that are metabolically inactive outside the host and after accessing the host cell becomes activated (Dupre & O'Malley, 2009) . They are comprised primarily of proteins and nucleic acid; the proteins contribute to their unique shape by forming a capsid (Andersson, 2010) . Therefore, viruses are of different forms, like superficial, helical, icosahedral, or complex, and perhaps some viruses are accompanied by a lipid bilayer extrapolated from a host membrane called an envelope (Geng et al., 2007) . Besides, capsid proteins associated with nucleic acids form nucleocapsids. Proteins related to viral nucleic acids are called nucleoproteins. Virus nucleic acid is either DNA or RNA and has been the elementary source of knowledge required to monitor its metabolic functions. This DNA and RNA are categorized based on the number of strands into single or doublestranded DNA/RNA (Firth et al., 2010; Pichlmair et al., 2006) . The sense of strand can further differentiate single-stranded RNA viruses as some RNA viruses have a positive-sense RNA (+ve ssRNA), and some viruses have a negative-sense RNA (−ve ssRNA) (Gorbalenya, Enjuanes, Ziebuhr, & Snijder, 2006) . Nucleic acid form (DNA/RNA) is indeed a vital point of differentiation since all viruses did not constitute the same nucleic acid pattern (Gao & Hu, 2007) .

The multiplication of all viruses results from several sequential processes: adhesion of the virus to the cell surface, virus adsorption and entry into the cell, replication of viral nucleic acids, and expression of viral proteins, and release of virus particles from the cell. For example, the virus entrance process is often carried out by cell surface proteins; Hepatitis C virus (HCV) entry involves claudin-1, occludin, and tetraspanins as the primary receptor proteins (Burlone & Budkowska, 2009 ). The latter's accession is influenced by other lipoproteins and the enzyme lipoprotein lipase. Moreover, infection with the influenza virus is modulated by a protease enzyme that triggers the viral surface protein hemagglutinin (Zambon, 2001) . The protease enzyme is pertinent for illustrating viral proteins; it categorizes proteins into groups based on everyone's structural and non-structural features (Appel, Schaller, Penin, & Bartenschlager, 2006) . But RNA viruses require two powerful enzymes to sustain; reverse transcriptase and integrase, former transcribed viral RNA to DNA at the moment of replication (Briones, Dobard, & Chow, 2010; Sluis-Cremer & Tachedjian, 2008) . In contrast, the second enzyme integrates viral DNA into the host genome and is required for the effective uncoating of virus-core proteins. As a result, the virus needs enzymatic and non-enzymatic proteins to stop its replication and infection.

Conventional medicine is indeed a worthwhile line of study for analyzing, extracting, and developing medicinal benefits. Conversely, a relatively small proportion of bioactive compounds were studied systematically for their therapeutic uses. Natural products include an unusual approach to exploring antiviral agents with remarkable pharmacological properties (Cragg & Newman, 2013; Atanasov et al., 2015) . Herbal therapists have been using traditional plants since prehistoric days to cure diseases in humans and animals, particularly in the Asia-Pacific region. People continue to rely on medicinal herbs and their products for their wellness and primary medical care throughout the globe (Ekor, 2014) . About 2,500 natural plant species are listed globally to diagnose many diseases and illnesses (Kapoor, Sharma, & Kanwar, 2017) .

Collecting traditional data from local or indigenous communities or even using important ethnopharmacology plant(s) to extract bioactive molecules/phytochemicals is a very demanding approach for diagnosing different ailments (Altemimi, Lakhssassi, Baharlouei, Watson, & Lightfoot, 2017) . Numerous aspects, including the various solvents (polar, non-polar) used during the extraction of bioactive constituents and the selection of plant parts/tissue for their extraction from plants, commonly play a crucial role (Ben-Shabat, Yarmolinsky, Porat, & Dahan, 2020) . A holistic approach for isolating and characterizing bioactive molecules and virus replication inhibitory experiments in animal cell systems is required when such bioactive molecules could be used to cure a viral infection (Kapoor et al., 2017) . The eternal objective of establishing high throughput screening assays is just the way to recognize bioactive molecules/phytochemicals from large chemical libraries quickly and accurately. In vivo experiments and consequent clinical studies are necessary to identify the antiviral activity and severe complications like reactogenicity or toxicity of purified bioactive molecules.

Coronavirus (CoV) is a single-stranded, positive-sense envelope (ss-RNA) virus (Family: coronaviridae). The CoV family comprises many species responsible for causing respiratory and gastrointestinal infections in mammals and birds. It mostly leads to cold or flu in human beings, yet complications could emerge, such as pneumonia and severe acute respiratory syndrome (SARS) ( Van-der Hoek, 2007) . The documented CoV (HCoV) comprises HCoV-229E, -OC43, -NL63, -HKU1, and the universally recognized severe acute respiratory coronavirus syndrome (SARS-CoV), which triggered a high mortality threat to the world in 2003 (Geller, Varbanov, & Duval, 2012 (Hu, Azhar, Madani, & Ntoumi, 2020) . The virus seems to have a 96% resemblance to the coronavirus bat, and therefore it is generally believed to emanate from bats. There seem to be no precise medications or treatment options for COVID-19; however, numerous clinical trials assessing possible treatments are continuing during this period (WHO, 2020).

Coronaviruses are large pleomorphic spherical particles with a bulbous surface projection. The diameter of the virus particles is approximately 120 nm (Fehr, Perlman, Maier, Bickerton, & Britton, 2015) . The virus membrane in electron micrographs did appear as a unique pair of thick electron shells. The viral envelope consists of a lipid bilayer under which the membrane, envelope, and spike structural proteins are situated. A beta coronavirus subgroup A have a shortened spike-like surface protein called hemagglutinin esterase (HE) (Neuman, Kiss, Kunding, Bhella, & Baksh, 2011) .

Moreover, nucleocapsid develops copies of the nucleocapsid protein attached to the positive-sense single-stranded RNA genome (Fehr et al., 2015) . The genome size for coronaviruses ranges from 27 to 34 kilobases, the largest among documented RNA viruses. The lipid bilayer envelope, membrane protein, and nucleocapsid safeguard the virus outside the host cell (Neuman et al., 2011) . There is only one amino acid variation in specific genome sequences among viruses discovered in pangolins and viruses found in humans.

Interestingly, about 92% of the genetic material accessed between pangolin coronavirus and SARS-CoV-2 has been identified as a complete genome comparison to date that is grossly inadequate to demonstrate that pangolins are intermediate hosts (Cyranoski, 2020) . The virus does have a 96% resemblance to the coronavirus bat, and therefore it is generally believed that it emanates from bats (Cohen, 2020) .

The name coronavirus is derived from the Latin word corona, which means "crown" or "halo," which pertains to the characteristic appearance of the crown or solar corona around the virions (virus particles) under two-dimensional electron microscopy, due to the surface covering of the club-shaped protein spikes.

There have been no specific treatments for CoV infection, and preventive vaccines are still under examination. It illustrates the need to implement new antivirals for prophylaxis and treatment of CoV infection.

The complete list of the potent plant extracts and their bioactive compounds that inhibit coronavirus are depicted in Table 1 . Ginsenoside Rb1 (Gynosaponin C), one of the bioactive ginsenosides extrapolated from Panax ginseng, displayed antiviral activity (Wu et al., 2004) . Tetra-O-galloyl-beta-D-glucose, luteolin, and tetra-O-galloyl-beta-D-glucose, blocked the SARS-CoV host cell entry (Yi et al., 2004) . Chinese herbs have long been known for their antiviral effects and therefore examined for SARS-CoV's potential role. Of the 200 herbal extracts analyzed, Lycoris radiata, Artemisia annua, Pyrrosia lingua, and Lindera aggregata seemed to have an anti-SARS-CoV impact with a 50% effective aa(EC 50 ) of 2.4-88.2 μg/ml (Li et al., 2005a) . Additionally, tannic acid, 3-isotheaflavin-3-gallate, and theaflavin-3,3 0 -digallate, three black tea phenolics, collectively, exhibited inhibitory effects SARS-CoV 3CLpro with IC 50 values of 3, 7, and 9, 5 μM, respectively . On the other hand, phenolic compounds from Isatis indigotica showed an inhibitory effect against SARS-CoV 3CLpro with IC 50 values of 217, 752, 8.3, 365, and 1,210 μM, respectively for sinigrine, indigo, aloe emodin, hesperetine, and β-sitosterol .

Saikosaponins (A, B2, C, and D), naturally occurring triterpene glycosides obtained from Bupleurum spp., Heteromorpha spp., and Scrophularia scorodonia, exhibited antiviral activity against HCoV-22E9. Saikosaponin A, B2, C, and D have efficacy toward human CoV-229E, with EC 50 values of 8.6, 1.7, 19.9, and 13.2 μM, respectively; saikosaponin B2 subdued viral attachment and penetration stages (Cheng et al., 2006a) . These natural compounds effectively avoid the initial stage of HCoV-22E9 infection, like viral attachment and penetration, following co-challenge with the virus. In contrast, Rheum officinale, Polygonum multiflorum, and emodin have been investigated and proven to suppress SARS-CoV (S) protein and ACE2 interaction with IC 50 valuesHo et al., 2007) . Among 221 phytochemicals studied against SARS-CoV, 10 diterpenes, two sesquiterpenes, two triterpenes, and five lignans curcumin exhibited inhibitory effects at 3-10 μM concentration (Wen et al., 2007) .

Interestingly, psoralidin showed a strong protease inhibitor influence on SARS-CoV with an IC 50 value of 4.2 μM. Simultaneously, emodin, rhein, and chrysin hindered SARS-CoV (S) and ACE2 proteinprotein interaction at 0-400 μM (T. Y. Ho et al., 2007; Kim et al., 2007) . Conversely, ferruginol, 8β-hydroxyabieta-9(11),13-dien-12-one, 3β,12-diacetoxyabieta-6,8,11,13-tetraene, betulonic acid, betulinic acid, hinokinin, savinine, and curcumin inhibits replication of SARS-CoV at 0-80 μM (Wen et al., 2007) . Other natural anti-CoV molecules include water extract from Houttuynia cordata, which displayed antiviral mechanisms against SARS-CoV, such as viral 3CL protease inhibition and viral RNA-dependent polymerase activity blockage (Lau et al., 2008) . In the same way, Toona sinensis aqueous leaf extract inhibited SARS-CoV replication with EC 50 values ranging from 30 to 40 μg/ml and SI values ranging from 12 to 17 (Chen et al., 2008) . Procyanidin A2, procyanidin B1, and cinnamon tannin B1, extracted from Cinnamomi cortex, also hindered SARS-CoV infection at 0-500 μM (Zhuang et al., 2009) . Flavones and biflavones isolated from Torreya nucifera exude cytotoxic effect on SARS-CoV 3CLpro , and Tylophorin and 7-methoxycryptopleurine isolated from Tylophora indica inhibit both N and S protein function and viral replication of enteropathogenic coronavirus transmissible gastroenteritis virus (Yang et al., 2010) . Such molecules showed incredible antiviral activity with IC 50 values of 0.018 and <0.005 μM, respectively.

Tylophorine and 7-methoxycryptopleurine separated from T. indica have been shown to impede viral replication in coV-infected swine testicular cells (Yang et al., 2010) . Six plant extracts (Gentiana scabra, Dioscorea batatatas, Cassia tora, Taxillus chinensis, Cibotium barometz) asserted inhibitory effect against SARS-CoV 3CLpro with IC 50 values of 39 and 44 μg/ml, respectively (Wen et al., 2011) . Besides, diterpenoid, 8b-hydroxyabieta-9 (11), 13-dien-12-one, and lignin, savinin were reported to prevent SARS-CoV 3CLpro activity with a SI >667. In comparison, betulinic acid and savinin were found com- 2016). Note that the SARS-CoV spike protein (S) uses ACE2 as a responsive binding site to invade host cells ( Li, 2016) . HSV infection causes mucosal lesions in the ocular/perioral (usually HSV-1) and genital (usually HSV-2) areas and many other body sites.

HSV tends to cause lifetime infection by developing itself on the sensory neurons and thus can be reactivated by different stimuli, like sun exposure, sore throat, immune suppression, menstrual cycles, or anxiety (Fatahzadeh & Schwartz, 2007) . The transmission of HSV results from direct contact with infected lesions and could occur via vertical transmission from infected mother to fetus. However, the disease is typically self-limited and can be handled with antiviral drugs. However, consequences could develop in neonates, and immunosuppressed persons lead keratoconjunctivitis and life-threatening meningitis (Arduino et al., 2008; Chentoufi & Benmohamed, 2012) .

Hardly any vaccine is recommended against HSV, even though there are no effective drugs that could neutralize innate HSV infection. A few primary and metastatic conditions could be monitored by analogous like acyclovir, penciclovir, and prodrugs. Moreover, the expansion of resistance to antibiotics virus is becoming a severe problem, especially in immune-compromised patients (Morfin & Thouvenot, 2003) . Therefore, the discovery of new anti-HSV agents with diverse mechanisms is significant to HSV's clinical management.

Plant extracts attracted substantial attention while looking for alternative compounds with anti-herpetic activity. Intriguingly, innumerable plant-derived extracts and molecules were already known to prevent HSV replication (Table 2 ) (Akram et al., 2018; Li et al., 2017) .

Licorice roots of Glycyrrhiza glabra were used to prepare a 2% topical acid cream, which contains carbenoxolone sodium. The cream was used to cure12 patients having acute oral herpetic (HSV) infections. The disease symptoms such as pain and dysphagia were resolved after applying the cream six times a day within a short span of 24-48 hr. In contrast, ulceration and lymphadenopathy were shown to cure steadily within 24-72 hr (Partridge & Poswillo, 1984) .

Samarangenin B extracted from the leaves of Limonium sinense observed suppression of HSV-1 α gene expression (Kuo et al., 2002) .

Further, Artocarpus lakoocha containing oxyresveratrol was reported to prevent early and late HSV-1 and HSV-2 viral replication phases, respectively (Chuanasa et al., 2008) . Pterocarnin A compound isolated from Pterocarya stenoptera impeded HSV-2 from adhesion and infiltration to host cells . Yatein extracted from

Chamaecyparis obtuse substantially inhibits HSV-1 replication in HeLa cells without noticeable cytotoxic effects (Kuo et al., 2006) .

In comparison, several H. cordata flavonoids were assessed to determine their capability to obstruct the HSV-2 replication cycle. The principal flavonoids quercetine, quercitrine, and isoquercitrine showed significant HSV-2 activity . Subsequent investigation assessed that the mode of action could be behind the antiherpetic activity of H. cordata, like adsorption, entry, post-infection by NF-kB, and virucidal activity (Hung et al., 2015) . Also, meliacin obtained from Melia azedarach was shown to induce TNF-α and IFN-α production and reduce HSV-2 by improving virus-induced pathogenesis in the mouse genital model of herpetic inflammation (Petrera & Coto, 2009 ).

Comparably, the aqueous extract from Rhododendron ferrugineum blackberry extract and the extract from Myrothamnus flabellifolia enriched with proanthocyanidin prevented the HSV-1 infection (Danaher et al., 2011; Gescher, Kuhn, Lorentzen, et al., 2011) . Glucoevatromonoside, a cardenolide from Digitalis lanata, alter the cellular electrochemical gradient and hinder the proliferation of HSV-1 and HSV-2 in cells (Bertol et al., 2011) . The natural products from the marine ecosystem such as algae and sponges produce active metabolites with anti-HSV activity (Sagar et al., 2010; Vo et al., 2011) . Houttuynoids A-E extracted from H. cordata, showed effective anti-HSV-1 activity (Chen et al., 2012a) .

Another resveratrol compound isolated from the Veratum grandiflorum inhibited NF-kB activation, the primary bioactive substance present in grapes, peanuts, legumes, or other plant-derived matrices and perhaps in red wine (Chen et al., 2012b) .

Numerous studies documented the antibacterial activity of resveratrol against the ACV-resistant and wild-type HSV-1 and HSV-2 replication cycles in cell lines and animal studies (Faith et al., 2006; Leyton et al., 2015) . Compounds like spiroketalenol ether derivatives extracted from Tanacetum vulgare rhizome extract served as cell entry inhibitors and apprehend HSV-1 gC and HSV-2 gG glycoproteins production (Alvarez et al., 2015) . Essential oils derived from Glechon spathulata and Glechon marifolia noted antiviral activity against HSV-1, which became effective after infecting Vero cells (Venturi et al., 2015) . Furthermore, essential oils derived from plants of the families Labiatae and Verbenaceae have an antiviral effect on HSV.

Vero cells after incubation with HSV and essential oils for 48-72 hr dramatically lowered viral titers of HSV-1 and HSV-2. It is important to note that their modes of action were related to the pre-infective stages (Brand et al., 2016 ). An analysis showed that the leaves of Further, 12 compounds isolated from Eucalyptus globulus leaves and twigs were noticed to have antiviral efficacy against HSV-1 and HSV-2. Tereticornate A has been assessed to holds the most incredible action against HSV-1, relatively high than acyclovir. Cypellocarpin C showed significant antiviral activity against HSV-2, higher than that offered by acyclovir (Brezáni et al., 2018) . Organic extracts relating to the Peganum harmala species showed antiviral activity against HSV-2 by disrupting virus entry (Benzekri et al., 2018) . Besides, Yatein separated from C. obtuse prevents HSV-1 alpha gene expression, along with ICP0 and ICP4 expression of genes, by halting HSV-1 DNA replication and structural protein expression in HeLa cells . Natural anti-HSV substances' availability should provide novel pharmacological properties against the virus for future use in monitoring HSV infections. phyllanthine, flavonoids (ternatin), and alkaloids such as quercetin.

They can block the endogenous DNA polymerase enzyme of HBV, which is crucial for viral replication (Venkateswaran et al., 1987) . A variety of bioactive metabolites extracted from Phyllanthus niruri were also evaluated for their inhibitory potential, using sera containing HBsAg, collected from chronic HBV patients (Thyagarajan et al., 1982) . Subsequent studies have revealed the in vivo efficiency of P. niruri extract in eliminating HBV in 3-6 weeks in mammals. A 90-day treatment with plant extracts successfully reduced the HBV antigen to undetectable levels among two-thirds of HBV-positive patients (Wang et al., 1995) . Further, numerous studies were conducted in the last several years to recognize anti-HBV molecules from medicinal herbs (Cui et al., 2010; Qiu et al., 2013; Zhan et al., 2010; Zhang et al., 2010) . There seems to be a lack of studies on bioactive components' mode of action against HBV, while most natural compounds were proven to effectively suppress the HBV (Wu, 2016) (Table 3) . For instance, Acanthus ilicifolius L. significantly decreases HBV-induced liver damage by lowering the transaminase (Wei et al., 2015) .

Gymnema sylvestre phytoconstituents prevent HBsAg binding and HBV DNA polymerase activity (Subashini and Rajendran, 2015) . Their probable anti-HBV mode of action was expected by the ability to bind with viral Pol/RT and core as well as host NTCP proteins (Parvez et al., 2020) .

Radix isatidis were mediated by the stimulation of the IFNα-dependent JAK/STAT signal pathway and the initiation of protein expression against HBV (Wang et al., 2020) . Swertisin obtained from

Iris tectorum displayed a significant inhibitory effect for HBV replication by inhibiting HBeAg and HBsAg and HBV DNA .

Although novel anti-HBV inhibitors were developed, the combination of remedies with conventional nucleotide/nucleoside analogs or IFNα-based hepatitis B therapy must also be assessed in future research. transplantation (Welsch et al., 2012) . The rapid expansion of anti-HCV substances is indeed essential to address such deficiencies. (Polyak et al., 2007 (Polyak et al., , 2010 . Many clinical trials showed a viable impact on reducing the viral load (Marino et al., 2013; Neumann et al., 2010) . Curcumin was reported as a critical inhibitor of HCV replication by conceivably restricting the sterol regulatory elementbinding to protein-1 (SREBP-1)-Akt pathway Kim et al., 2010) , and its T A B L E 3 Antiviral effects from several potent natural products/extracts against specific viruses 

adverse impact on HCV entry (Anggakusuma et al., 2013) . Many natural products deter HCV entry, including epigallocatechin-3-gallate, griffithsin, ladanein, and tellimagrandin I (Calland et al., 2012; Ciesek et al., 2011; Haid et al., 2012; Meuleman et al., 2011; Takebe et al., 2013) . Similarly, chebulagic acid and punicalagin hydrolyzable tannins were found as competitive HCV intake inhibitors . (Sierra et al., 2005) . It is transmitted through an interchange of viruses containing blood and fluids, like sexual intercourse, the sharing of infected needles/sharp objects, and breastfeeding (Shaw & Hunter, 2012) . HIV is the principal cause of acquired immunodeficiency syndrome (AIDS), the gradual incompetence of the immune cells due to CD4+T lymphocyte deterioration, leading to life intimidating infectious disease and autoimmune disorders (Moss, 2013) .

Amidst approximately 30 years of scientific research ever since its exploration, there's still currently no specific preventative medicine or remedy for HIV infectious diseases. The high antigenic variability and myriad pathways used by the virus to undermine the immune system's appreciation have made prophylactic/therapeutic management of HIV infection complicated (Burton et al., 2004) . Interestingly, the development of highly active antiretroviral therapy (HAART), consisting of a cocktail of nucleoside analog/non-nucleoside reverse transcriptase inhibitors, has significantly decreased the mortality rates associated with HIV/AIDS (Ghosh et al., 2011) . However, there is still an urgent need for adequate therapeutic approaches against HIV infection related to drug resistance development, accompanying toxicity treatment, patient adherence, and inadequate access in resourcepoor areas (Piot & Quinn, 2013) . A comprehensive list of herbal ingredients for HIV infection was examined (Cos et al., 2008; Singh & Bodiwala, 2010) (Table 3 ). In contrast, marine products with anti-HIV activity were reported as potential anti-HIV treatment X. Zhou et al., 2013) .

Phytolacca americana is a potent source of a set of plant proteins known as pokeweed antiviral protein (PAP). Three isoforms, specifically from spring leave PAP-I, early summer leaves PAP-II, and late summer leaves PAP-III was identified as a class of ribosomeinactivating proteins (RIPs) responsible for causing depurination of genomic HIV-1 RNA (Rajamohan et al., 1999) . Similarly, Momordica charantia and Gelonium multiflorum are considered useful sources of an anti-HIV protein MAP30 and GAP31, similar to RIPs known for their anti-HIV potency (Schreiber et al., 1999) .

Furthermore, the leaves of P. americana also contain an anti-HIV protein PAP29, having a prophylactic anti-HIV potential. P. Wang and Tumer (1999) reported that PAP isolation cleaves supercoiled DNA into linear and straightforward forms using the same active site required to remove rRNA purine. The RIPs are toxic N-glycosidases that purify the typically preserved α-sarcin loop of large rRNAs. Thus, depuration disables the ribosome, consequently obstructing its further involvement in protein synthesis. Several studies have shown that RIP's enzymatic activity is not only restricted to site-specific activity on ribosome rRNAs but also entails the depuration and nucleic acid scission of other targets (Barbieri et al., 2000; Horrix et al., 2011; Nicolas et al., 1998) . Trichobitacin, a RIP, extracted from the roots of Trichosanthes kirilowiiis was reported to decline the appearance of the p24 HIV-1 antigen by reducing the number of antigens in HIVpositive cells in an acute in vitro assay but failed in cases of chronic infection (Zheng et al., 2000) . Cyanovirin-N extracted from marine algae showed an inhibitory effect on HIV through aborting transmission and cell to cell fusion of HIV by interacting strongly with gp120 (De Clercq, 2000) . Several sulfated polysaccharide groups extracted from seaweeds possess anti-HIV effects by interfering with viral adsorption (Duarte et al., 2001; Schaeffer & Krylov, 2000) . Alkaloid extracts of P. niruri exhibited an inhibitory effect on HIV by monitoring the inhibition of HIV-induced cytopathogenecity in human MT-4 cells (Naik & Juvekar, 2003) . Furthermore, coumarin-containing calophyllum species exhibited an inhibitory effect on HIV (Cesar et al., 2011; Huerta-Reyes et al., 2004) . Similarly, the crude extracts of A. annua and Artemisia afra revealed promising anti-HIV efficacy (Lubbe et al., 2012) . In regards, tricyclic coumarin reported from Calophyllum brasiliense stem bark suppressed HIV replication by repressing the activation of nuclear factor-kappa B (NF-κB) in in vitro models (Kudo et al., 2013) . include fever, headache, sore throat, sneezing, and muscle and joint pain, which can lead to devastating and potentially lethal situations like pneumonia (Eccles, 2005; Rello & Pop-Vicas, 2009 ). IFA (most epidemics) has a broad array of hosts, such as birds, human beings, and other mammals. At the same time, IFB seems to harm people naturally, and IFCs could be separated from humans and pigs (Pleschka, 2013) . to infection. Another concern is the pervasive growth of drug resistance, mostly M2 ion channel blockers of amantadine and rimantadine, in the first wave of anti-influenza drugs. Resistant strains of available neuraminidase inhibitors such as oseltamivir and zanamivir (which mainly prevent the release of mature influenza viruses) have also been identified (Samson et al., 2013) . As a result of drug resistance development, the rapid evolution of influenza viruses, and the incidence of many recent outbreaks (e.g., H5N1, H1N1, H7N9), more advanced antiviral strategies are urgently needed to prevent and control potential pandemics with evolving influenza strains (Shao et al., 2017) . Numerous natural products have been assessed for their adverse effects on influenza (Table 3) .

Pelargonium estides root extract restricts IFA entry influences, viral hemagglutination, neuraminidase function, and improves influenza-infected mice (Theisen & Muller, 2012) . Aqueous extract from Taraxacum officinale inhibits IFA infection and reduces the activity of polymerase and nucleoproteins (NP) RNA levels (He et al., 2011) . Several plant secondary metabolites were also determined as possible inhibitors of NA influenza (Grienke et al., 2012) such as chalcones from Glycyrrhiza inflata ( Recently, a randomized trial of 312 Australian adults undertaking international travel by coach received black elder capsules 300 mg b.i.d. before travel and t.i.d. during travel and after arrival, or placebo.

Each participant took their assigned medicine for a total of 14 days.

There was no difference between the groups in terms of the incidence of clinical viral respiratory infections. However, these colds' duration was significantly shorter and severity substantially less in the black elder group than the placebo. There was no difference between the two groups' adverse effects, suggesting no significant danger from black elders (Tiralongo et al., 2020) . The development of these natural anti-influenza agents for clinical use will further extend the portfolio of drugs for prophylactic treatment of severe flu epidemics or pandemic.

Enterovirus 71 (EV71) is a pathogenic species of the Picornaviridae family. EV71 comprises a single positive RNA genome with approximately 7.5 kb. It was observed throughout a modest epidemic in California between 1969 and 1972 (Schmidt et al., 1974) . EV71 became the most infective enterovirus serotypes, causing several global outbreaks. EV71 inflammation develops rashes, and vesicular lesions on the hands, legs, and oral mucosa. It sometimes develops fatal congenital abnormalities such as aseptic meningitis, encephalitis, acute respiratory disease, and pulmonary edema. A fecal-oral route mainly delivers EV71, but transfer by a respiratory droplet is indeed conceivable. It's among the most prominent reasons for hand-foot and mouth disease (HFMD) in young kids, often associated with severe neurological disorders that can be devastating (Tapparel et al., 2013) . The risk of transmission in children below 5 years of age is reasonably high in endemic regions, and several epidemics had already happened during the last few millennia.

Preventive EV71 vaccines were currently developed, and palliative care is being used to improve the symptoms. However, many other natural products and herbal medicines exhibited inhibitory activity against EV71 infection (Table 3 ). The analysis revealed that O. basilicum extracts and isolated compounds effectively prevent EV71 disease and replication . In contrast, raoulic acid recognized as a CVB inhibitor suppresses EV71 (Choi et al., 2009) H. cordata found the only remedy with potent antiviral activity against both EV71. These study results may justify follow-up experiments to determine the precise molecular mechanisms of action and to analyze the plant's anti-EV71 capability in the animal study . (Hong et al., 2015; Song et al., 2014) . Without appropriate medical care to prevent and treat EV71 infection, further studies are needed to explore novel enteroviral antivirals.

RSV is an enshrouded negative-stranded ssRNA virus belonging to the Paramyxoviridae family. RSV is a prevalent virus responsible for respiratory illness in infants and toddlers (Hall, 1994) . Almost all children often get afflicted with RSV well before 2 years (Braciale, 2005) .

and immunocompromised patients (Sigurs et al., 2005) . Even though RSV causes the most severe illness in premature children, it continues to haunt living beings throughout their lifespan. Immune response to RSV is usually not sufficient to provide protection, but instead, humans are susceptible to reiterated re-infections (Hall et al., 2009; Henderson et al., 1979) , that may be life-threatening for older or immune-compromised patients (Falsey & Walsh, 2000) . Presently, RSV immunotherapy is not applicable. The therapies available for diagnosing RSV infections like palivizumab (a monoclonal antibody against RSV fusion protein) and ribavirin (nucleoside analog) are slightly effective. Therefore, it is necessary to develop new antivirals to manage RSV infections, and numerous plant-derived natural products were shown to display anti-RSV activity (Table 3) .

Uncinoside A and B, the two isolated chromone glycosides from Selaginella uncinata, effectively inhibit RSV inflammation, and biflavonoids, namely genkwanol B, genkwanol C, and stellenranol derived from Radix Wikstroemiae, are said to have antiviral activity against RSV (Huang et al., 2010; Ma et al., 2003) . Further, flavonous 6-C-monoglycosides from Lophatherum gracile leaves reported curtailing RSV infection in the cytopathic impact reduction assay (Wang et al., 2012c) . Numerous natural anti-RSV therapies such as the herbal prescription (Cimicifuga foetida L., and bioactive compound cimicifuga) relieve respiratory diseases Wang, Ho, et al., 2012; Wang, Chen, et al., 2012) . Furthermore, chebulagic acid and punicalagin hydrolyzable tannins possess antiviral activity toward RSV infection. The two tannins can explicitly inactivate RSV entities and obstruct viral entry aspects, like binding and fusion. They are inadequate against the transmission of RSV post-infection and could contravene the same event in MV, which is another paramyxovirus . Certain herbal products will help improve the respiratory tract symptoms induced by RSV, like inflammation of the respiratory system to target the viral infection. Resveratrol is one specific illustration documented to stabilize IFN-γlevels and prevent the trachea's inflammation/hyperresponsiveness throughout RSV infection in mice, implying its suitability to minimize airway symptoms triggered by RSV (Zang et al., 2011) . Tangeretin and nobiletin (polymethoxylated flavones) obtained from Citrus reticulate (Pericarps)

impaired RSV replication intracellularly. Tangeretin significantly suppressed RSV phosphoprotein (P protein) expression through viruscell fusion inhibition at an early stage and cell fusion inhibition at the end of the replication process (Xu et al., 2014) . Schefflera heptaphylladerived dicaffeoylquinic acids also hindered RSV replication (Li et al., 2005b) . The ethanol extract of Lophatherum gracile suppressed RSV infection and inflammation prompted in a dose-dependent manner (Chen et al., 2019) .

Rotavirus is the common cause of chronic gastroenteritis in infants and young children across the globe. It is a paramount public health concern in low-income countries and massive morbidity and mortality rates in advanced nations (Parashar et al., 2006) . The genus of rotavirus consists of nine species (A to I), but the only rotavirus A tends to cause more than 90% of human rotavirus infections (Kirkwood, 2010 (Ramig, 2007; Rivero-Calle et al., 2016) .

While there is no particular antiviral drug for rotavirus, several other preventative actions like environmental hygiene and safe food and water can reduce the risk of rotavirus infection (Brown et al., 2013) . The U.S. Food and Drug Administration (FDA) certified two subsequent oral attenuated vaccines as an efficient way to prevent rotavirus pandemics. The RotaTeq (Merck), a pentavalent human-bovine vaccine is comprising four rotavirus strains generated by recombination and Rotarix (GlaxoSmithKline), a monovalent human rotavirus vaccine that included one G1P-specific rotavirus strain (Desai et al., 2012; Gurgel et al., 2011) . Hence, alternative safe therapies for rotavirus infections have become the subject of ongoing research (Alfajaro et al., 2014) . Pinus koraiensis, Lomatium dissectum, Artocarpus integrifolia, Myristica fragrans, Spongias lutea, Tylosema esculentum, Byrsonima verbascifolia, Myracrodruon urundeuva Allemão, Eugenia dysenterica, Hymenaea courbaril, and Achillea kellalensis were reported to hinders rotaviral strains (Cecílio et al. 2012; Chingwaru et al. 2011; Gandhi et al., 2016; Goncalves et al., 2005; Taherkhani et (Birdi et al., 2011; Brijesh et al., 2009; Civra et al., 2017; El-Baz et al., 2015; Knipping et al., 2012; Mohamed et al., 2015; Pilau et al., 2011; Roner et al., 2010; Téllez, Téllez, Vélez, & Ulloa, 2015) . Besides, Vaccinium macrocarpon, Vitis labrusca, and Myracrodruon urundeuva (Cecílio et al., 2016; Lipson et al. 2007 Lipson et al. , 2011 Lipson et al. , 2012 fever, malaise, rash, and common colds. However, more severe forms could lead to nervous system diseases, such as aseptic meningitis, encephalitis, and paralysis (Tapparel et al., 2013) . CVA is best known as one of the causative agents of HFMD in young children, and CVA group 16 strain (CVA16) is the predominant causative agents of HFMD among CVA .

Unfortunately, hardly any vaccine or effective antibiotic treatments are presently available to avoid CV infections. However, natural ingredients, herbs, and traditional decoctions showed CV-infection therapy (Table 3) . A study performed on 76 patients treated with Sophora spp. extract reported that RNA clearance of Coxsacki B virus was dose-dependent, and all patients displayed relief from arrhythmia, improved cardiac output, stroke volume, and cardiac index showed progress. The left ventricular mass and its index diminished expressively. The anti-Coxsackie antibody returns to the average titer after 5-months of treatment (Li, 1996) .

Aqueous, ethanol extract and bioactive compounds, such as linalool, apigenin, and ursolic acid from Ocimum basilicum (sweet basil)

reported antiviral activity against CVB1. In particular, Ursolic acid interacts with post-infection replication of CVB1 .

Further, Bupleurum kaoi was known to inhibit CVB1 infection by activating type I interferon response (Cheng et al., 2006b; Cheng et al., 2007) . Raoulic acid from Raoulia australis was determined as an antiviral informant against many CVB subtypes; however, the mechanism for its influence is uncertain (Choi et al., 2009) . Rheum palmatum (Polygonaceae) against CV B3 in vitro and in vivo showed inhibitory effects on HEp-2 cells. Extract-treated mice showed improved survival rate, reduced clinical symptoms, and lowered viral titers. The whole study demonstrates that interferon inducers of type I could be useful in maintaining CVB infection and could be further analyzed as a therapeutic intervention (Xiong et al., 2012) . Besides, extracts of Dodonaea viscosa leaves displayed a therapeutic efficacy ranging from 0.3 to 25 with a reduction in virus titer ranging from 0.25 to 5 log10 TCID 50/0.1 ml against coxackievirus B3 (CVB3) infections. Crude extract provided significant inhibition of CVB3 replication by attaching to the viral capsid of CVB3, and prevents the virus from accessing host cells (Shaheen et al., 2015) . Cornus officinalis, Acer triflorum, Pulsatilla koreana, and Clematis heracleifolia var. Davidiana

Hemsl extracts showed significant antiviral activity toward CVA16 . Isatindolignanoside A, a glucosidic indole-lignan isolated from aqueous root extract of Isatis indigotica revealed antiviral activity against CVB3 CVB3, with IC 50 and SI values of 25.9 μM and >3.9, respectively (Meng et al., 2018) .

DENV is an encased positive sensory ssRNA virus of the Flaviviridae family. The DENV is transferred particularly by mosquito bites of Aedes aegypti and is an influential arbovirus in Southeast Asia (Black et al., 2002) . However, most of the four virus serotypes (DENV 1-4), could trigger dengue fever (Back & Lundkvist, 2013) . Clinical symptoms of DENV infection include evident/mild febrile exposure, contemporary dengue fever (fever, headache, myalgia, joint pain, nausea, vomiting, and skin rash), and life-threatening hemorrhage diseases, explicitly dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) (Sam et al., 2013) . Although this is an obsolete viral infection, current vaccination and treatment interventions accessible to prevent and control DENV infection are minimal. The management of dengue-related illnesses entails mosquito-controlled viral infection prevention and the alleviation of infected patients' symptoms.

Developing preventative/pharmacological intervention for DENV infection with natural ingredients could resolve these practical limits.

Quite a few natural compounds, like quercetin and narasin, and marine algae derivatives exhibit robust anti-DENV features (Zandi et al., 2011; Low et al., 2011; Koishi et al., 2012) (Table 3) . For example, Flavone baicalein shows inhibitory activities against DENV adsorption to host and post-entry viral replication (Zandi et al., 2012) .

Also, chebulagic acid and punicalagin, extracted from Terminalia chebula, have a broad array of antiviral agents against the viruses . They will effectively inactivate free DENV particles and tamper with attachment and fusion incidents throughout the early viral entry. Nordihydroguaiaretic acid extracted from the leaves of 

MV is an encased negative-sense ssRNA virus of the Morbillivirus gene (Family: Paramyxoviridae). MV induces measles (an acute respiratory infection characterized by fever, conjunctivitis, coughing, runny nose, and nausea), and a generalized red macular rash across the body resulting in pneumonia encephalitis (Sabella, 2010) . Although extremely infectious by interaction with respiratory secretions or airborne particulates, immunotherapies toward measles were described as a three-part MMR vaccine (measles, mumps, and rubella). Despite an effective MV vaccine, the virus remains a vital assassin for children in the developing world (Clements & Cutts, 1995; Murray & Lopez, 1997) . A severe further aspect is a resurgence of measles in vaccinated populations and non-immunized individuals (Mossong & Muller, 2003; Zandotti et al., 2004) . Such problems highlight MV's medical significance and the need to develop appropriate drug therapies.

Natural products from East and South-east Asian medicinal plants (Kurokawa et al., 1993) , the herbal decoction (Huang et al., 1997) , the Cherokee remedy spicebush (McWhorter, 1996) , plant bioflavonoid isolated from Rhus succedanea and Garcinia multiflora (Lin et al., 1999) , calcium spirulan from the blue-green alga Spirulina platensis (Hayashi et al., 1996) and several Rwandan and Ugandan medicinal plant extracts were reported to inhibit MV infection (Cos et al., 2002) ( Table 3 ). In contrast, certain Olinia rochetiana (Olkirenyi) and

Warburgia ugandensis (Osokonoi) typical dietary herbal additives were demonstrated to suppress in vitro MV infection (Parker et al., 2007) .

Another example is the Cajanus cajan extracts recommended to have anti-MV activity, though their bioactive components remain unknown (Nwodo et al., 2011) . The chebulagic acid and punicalagin tannins showed potent efficacy against MV infection, mainly by inhibiting the virus particles, disrupting the attachment and fusion stages throughout viral entry . Therefore, they could serve as potential entry inhibitors to MV.

Antiviral drug production is a concern, as enzymes do not behave like normal living cells and antiviral medications could only deter replication of viruses or inhibit deeper inflammation. Accordingly, plant extracts/botanically derived compounds were documented with potential antiviral activity in cell line and animal model studies. Intriguingly, different mechanisms were established for these compounds, among which virucidal behavior is the most prevalent. Other confirmed exercises include hindering virus entrance into target cells, inhibiting viral protein expressions like 3CLpro, PLpro, S, and ACE2, and interfering with viral DNA replication, all of which are essential prerequisites constructing individual viral particles. Besides, the introduction of high-throughput technologies and traditional medicines together might play a critical role in assessing potential plant-derived substances for innovative discovery in contemporary drug development. They compete against viral diseases but have a long way to go before final use in the clinic to compensate for exploration, isolation, and mechanistic studies. Given the broad diversity of bioactive molecules derived from plants, a reliable, relentless, and constant approach is necessary to pursue unidentified bioactive molecules with potent antiviral activity, particularly relative to the risk posed by pathogenic viruses to enhance resistance to antibiotics. Many natural products like lycorine, homoharringtonine, silvestrol, ouabain, tylophorine glycyrrhetinic acid, acetoxime, and caffeic acid chebulagic acid, punicalagine and 7-methoxycryptopleurine possess significant antiviral activity even in the nanomolar concentration and will be better candidates for novel drug discovery. However, it requires further research to demonstrate the mechanism of secondary metabolites' action in an in vivo and invitro model.

In contrast, many natural products with good antiviral activity are the essential components of some traditional food additives that could strengthen the wider public's immune system in inevitable outbreaks. Further, research must entertain therapeutic agents' feasibility with several other natural sources or with existing drugs, as the multitarget treatment mitigating the chances of drug-resistant viruses being developed. Therefore, comprehensive research in the forthcoming could recognize the possible antiviral molecules and understand their mechanism of action to stabilize such fatal viruses more appropriately.

The authors declare no conflicts of interest.

No data are available to share.

Venugopalan Venkatesalu https://orcid.org/0000-0002-3753-8432

Moroccan Medicinal plants as inhibitors against SARS-CoV-2 main protease: Computational investigations

Antiviral activity of Eucalyptus camaldulensis leaves ethanolic extract on herpes viruses infection

Broad-spectrum antiviral agents: A crucial pandemic tool

Antiviral potential of medicinal plants against HIV, HSV, influenza, hepatitis, and coxsackievirus: A systematic review

Antiviral activity of the volatile oils of Melissa officinalis L. against Herpes simplex virus type-2

Anti-rotaviral effects of Glycyrrhiza uralensis extract in piglets with rotavirus diarrhea

Anti-rotavirus effects by combination therapy of stevioside and Sophora flavescens extract

Phytochemicals: Extraction, isolation, and identification of bioactive compounds from plant extracts

A spiroketal-enol ether derivative from Tanacetum vulgare selectively inhibits HSV-1 and HSV-2 glycoprotein accumulation in Vero cells

General polyhedra, virus structure and mutation

Herpes Simplex Virus Type 1 infection: overview on relevant clinico-pathological features

Turmeric curcumin inhibits entry of all hepatitis C virus genotypes into human liver cells

The promise of traditional medicines

From structure to function: New insights into hepatitis C virus RNA replication

Ethnobotanical study of plants used for the treatment of diarrhoea in the Eastern Cape

Study on antiviral activities, druglikeness and molecular docking of bioactive compounds of Punica granatum L. to Herpes simplex virus -2 (HSV-2). Microbial Pathogenesis

Discovery and resupply of pharmacologically active plant-derived natural products: A review

Dengue viruses-an overview

Pectic polysaccharides from Panax ginseng as the anti-rotavirus principals in Ginseng

Investigation of stilbenoids as potential therapeutic agents for rotavirus gastroenteritis

Intracerebral propagation of Alzheimer's disease: Strengthening evidence of a herpes simplex virus etiology

Antiviral activity of meliacine on the replicationof a thymidine kinase-deficient mutant of Herpes simplex virus type 1 alone and in combination with acyclovir

Polynucleotide: Adenosine glycosidase is the sole activity of ribosome-inactivating proteins on DNA

Bioactive compounds from Hypericum humifusum and Hypericum perfoliatum: Inhibition potential of polyphenols with acetylcholinesterase and key enzymes linked to type-2 diabetes

Infectious disease. Combating emerging viral threats

Antiviral effect of phytochemicals from medicinal plants: Applications and drug delivery strategies

Anti HSV-2 activity of Peganum harmala (L.) and isolation of the active compound

Antiherpes activity of glucoevatromonoside, a cardenolide isolated from a Brazilian cultivar of Digitalis lanata

The natural compound silvestrolis a potent inhibitor of Ebola virus replication

In vitro antigiardial and antirotaviral activity of Psidium guajava L. leaves

Antiviral drugs for cytomegalovirus diseases

Flavivirus susceptibility in Aedes aegypti

Hemidesmus indicus (L.) R. Br. Extract inhibits the early step of herpes simplex type 1 and type 2 replication

Common nodes of virus-host interaction revealed through an integrated network analysis

Respiratory syncytial virus and T cells: Interplay between the virus and the host adaptive immune system

Antiviral activity of Colombian Labiatae and Verbenaceae family essential oils and monoterpenes on Human Herpes viruses

Here a virus, there a virus, everywhere the same virus?

Anti-infectivity against herpes simplex virus and selected microbes and anti-inflammatory activities of compounds isolated from Eucalyptus globulus labill

Studies on the antidiarrhoeal activity of Aegle marmelos unripe fruit: Validating its traditional usage

Role of human immunodeficiency virus type 1 integrase in uncoating of the viral core

Water, sanitation, hygiene and enteric infections in children. Archives of Disease in Childhood

Hepatitis C virus cell entry: Role of lipoproteins and cellular receptors

HIV vaccine design and the neutralizing antibody problem

Epigallocatechin-3-gallate is a new inhibitor of hepatitis C virus entry

A screen of the NIH clinical collection small molecule library identifies potential anti-coronavirus drugs

Anti-dengue serotype-2 activity effect of Sambucus nigra leaves-and flowers-derived compounds

Screening of Brazilian medicinal plants for antiviral activity against rotavirus

Antiviral activity of Myracrodruon urundeuva against rotavirus

The characteristics of pandemic pathogens

Inhibition of HIV-1 reverse transcriptase, toxicological and chemical profile of Calophyllum brasiliense extracts from Chiapas

Ethanol extract of Polygonum cuspidatum inhibits hepatitis B virus in a stable HBV-producing cell line

Sho-saiko-to (Xiao-Chai-Hu-Tang) and crude saikosaponins inhibit hepatitis B virus in a stable HBV-producing cell line

Toona sinensis Roem tender leaf extract inhibits

Inhibition of SARS-CoV 3C-like protease activity by Theaflavin-3, 3 0 -digallate (TF3)

Isocorilagin, isolated from Canarium album (Lour.) Raeusch, as a potent neuraminidase inhibitor against influenza A virus

Antiviral activity of ethanol extract of Lophatherum gracile against respiratory syncytial virus infection

Anti-enterovirus 71 activities of Melissa officinalis extract and its biologically active constituent rosmarinic acid

A laboratory evaluation of medicinal herbs used in china for the treatment of hand, foot, and mouth disease

Houttuynia cordata blocks HSV infection through inhibition of NF-kB activation

Mechanism of action of the suppression of herpes simplex virus type 2 replication by pterocarnin A

Antiviral effects of saikosaponins on human coronavirus 229E in vitro

Xiao chai hu tang inhibits CVB1 virus infection of CCFS-1 c ells through the induction of Type I interferon expression

ent-Epiafzelechin-(4alpha-->8)-epiafzelechin extracted from Cassia javanica inhibits herpes simplex virus type 2 replication

Excoecarianin, isolated from Phyllanthus urinaria Linnea, inhibits herpes simplex virus type 2 infection through inactivation of viral particles

Houttuynoids A-E, anti-herpes simplex virus active flavonoids with novel skeletons from Houttuynia cordata

Inhibition of herpes simplex virus infection by oligomeric stilbenoids through ROS generation

Bupleurum kaoi inhibits Coxsackie B virus type 1 infection of CCFS-1 cells by induction of type I interferons expression

Mucosal herpes immunity and immunopathology to ocular and genital herpes simplex virus infections

Antiviral activities of extracts and selected pure constituents of Ocimum basilicum

Cytotoxicity and anti-hepatitis B virus activities of saikosaponins from Bupleurum species

Tylosema esculentum (Marama) tuber and bean extracts are strong antiviral agents against rotavirus infection

Evaluation of antiviral activities of Houttuynia cordata Thunb. extract, quercetin, quercetrin and cinanserin on murine coronavirus and dengue virus infection

Prevention of human enterovirus 71 infection by kappa carrageenan

Geranylated flavonoids displaying SARS-CoV papain-like protease inhibition from the fruits of Paulownia tomentosa

Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease

Effect of Korean red ginseng intake on the survival duration of human immunodeficiency virus type 1 patients

Antiviral activity of raoulic acid from Raoulia australis against Picornaviruses

In vitro antienterovirus 71 activity of gallic acid from Woodfordia fruticosa flowers

Protective effect of Panax notoginseng root water extract against influenza a virus infection by enhancing antiviral interferon-mediated immune responses and natural killer cell activity

Antiviral activity of ethanol extract of Geranii Herba and its components against influenza viruses via neuraminidase inhibition

Anti-herpes simplex virus (HSV-1) activity of oxyresveratrol derived from Thai medicinal plant: Mechanism of action and therapeutic efficacy on cutaneous HSV-1 infection in mice

Activity-based and fraction-guided analysis of Phyllanthus urinaria identifies loliolide as a potent inhibitor of hepatitis C virus entry

Extracts of Equisetum giganteum L and Copaifera reticulate Ducke show strong antiviral activity against the sexually transmitted pathogen herpes simplex virus type 2

The green tea polyphenol, epigallocatechin-3-gallate, inhibits hepatitis C virus entry

In vitro screening for antiviral activity of Turkish plants revealing methanolic extract of Rindera lanata var. lanata active against human rotavirus

The epidemiology of measles: Thirty years of vaccination

Wuhan seafood market may not be source of novel virus spreading globally

Further evaluation of Rwandan medicinal plant extracts for their antimicrobial and antiviral activities

Plant-derived leading compounds for chemotherapy of human immunodeficiency virus (HIV) infection-an update

Natural products: A continuing source of novel drug leads

Traditional Chinese medicine and related active compounds against hepatitis B virus infection

Mystery deepens over animal source of coronavirus

Antiviral effects of blackberry extract against herpes simplex virus type 1. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology

Xanthones from Polygala karensium inhibit neuraminidases from influenza A viruses

Chalcones as novel influenza A (H1N1) neuraminidase inhibitors from Glycyrrhiza inflata

The future of antivirals: Broadspectrum inhibitors

Broad-spectrum antiviral activity of the carbocyclic analog of 3-deazaadenosine

Current lead natural productsfor the chemotherapy of human immunodeficiency virus (HIV) infection

Approved antiviral drugs over the past 50 years

Flavonoids as noncompetitive inhibitors of Dengue virus NS2B-NS3 protease: inhibition kinetics and docking studies

All-cause gastroenteritis and rotavirus-coded hospitalizations among US children

Emerging and re-emerging infectious diseases

CYSTUS052, a polyphenol-rich plant extract, exerts anti-influenza virus activity in mice

Inhibitory effect of sulfated galactans from the marine alga Bostrychia montagneion herpes simplex virus replication in vitro

Varieties of living things: Life at the intersection of lineage and metabolism

Understanding the symptoms of the common cold and influenza. The Lancet Infectious Diseases

The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety

Antiviral, antimicrobial and schistosomicidal activities of Eucalyptus camaldulensis essential oils

Epidemiology of viral hepatitis and hepatocellular carcinoma

Breaking down the barriers to a natural antiviral agent: Antiviral activity and molecular docking of Erythrina speciosa extract, fractions, and the major compound

Resveratrol suppresses nuclear factor-kB in herpes simplex virus infected cells

Respiratory syncytial virus infection in adults

Human herpes simplex labialis

An overview of their replication and pathogenesis; section 2 genomic organization

Using time-structured data to estimate evolutionary rates of double-stranded DNA viruses

Hepatitis B: Epidemiology and prevention in developing countries

Medicinal plants and natural molecules with in vitro and in vivo activity against rotavirus: A systematic review

Formation of hepatitis B virus covalently closed circular DNA: Removal of genome-linked protein

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burdenof Disease Study

Human coronaviruses: Insights into environmental resistance and its influence on the development of new antiseptic strategies

Shape effects of filaments versus spherical particles in flow and drug delivery

Emerging patterns and implications of HIV-1 integrase inhibitor resistance. Current Opinion in Infectious Diseases

Inhibition of viral adsorption and penetration by an aqueous extract from Rhododendron ferrugineum L. as antiviral principle against herpes simplex virus type-1

Proanthocyanidin enriched extract from Myrothamnus flabellifolia Welw. exerts antiviral activity against herpes simplex virus type 1 by inhibition of viral adsorption and penetration

Recent advances in antiretroviral drugs

In vitro anti-rotavirus activity of some medicinal plants used in Brazil against diarrhea

Nidovirales: Evolving the largest RNA virus genome

Influenza neuraminidase: A druggable target for natural products

Ganglioside GMia on the cell surface is involved in the infection by human rotavirus KUN and MO strains

Impact of rotavirus vaccination on diarrhea mortality and hospital admissions in Brazil

Antiviral activity of the dichloromethane extracts from Artocarpus heterophyllus leaves against hepatitis C virus

Activities of Ficus fistulosa leave extract and fractions against Hepatitis C Virus. Procedia Chemistry

A plant-derived flavonoid inhibits entry of all HCV genotypes into human hepatocytes

Prospects for a respiratory syncytial virus vaccine

The burden of respiratory syncytial virus infection in young children

Hepatoprotective and antiviral properties of isochlorogenic acid A from Laggera alata against hepatitis B virus infection

18 βglycyrrhetinic acid inhibits rotavirus replication in culture

Lippincott's illustrated reviews: Micobiology

Calcium spirulan, an inhibitor of enveloped virus replication, from a blue-green alga Spirulina platensis

Anti-influenza virus effect of aqueous extracts from dandelion

The root extract of the medicinal plant Pelargonium sidoides is a potent HIV-1 attachment inhibitor

Respiratory syncytial virus infections, reinfections and immunity. A prospective, longitudinal study in young children

Potential uses of plant species of the coastal mediterranean region

Ethanol extracts of Cassia grandis and Tabernaemontana cymosa inhibit the in vitro replication of dengue virus serotype 2

Structure-activity relationship of immunomodulating pectins from elderberries

Structural characterization of bioactive pectic polysaccharides from elderflowers (Sambuci flos)

Antiviral effect of epigallocatechin gallate on enterovirus 71

Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction

Immunology in the clinic review series; focus on type 1 diabetes and viruses: Role of antibodies enhancing the infection with Coxsackievirus-B in the pathogenesis of type 1 diabetes

Coadministration of Hedera helix L. extract enabled mice to overcome insufficient protection against influenza A/PR/8 virus infection under suboptimal treatment with oseltamivir

Plant ribosome-inactivating proteins type II induce the unfolded protein response in human cancer cells

An extract from Taxodium distichum targets hemagglutinin-and neuraminidase-related activities of influenza virus in vitro

The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health-The latest 2019 novel coronavirus outbreak in Wuhan

Genistein inhibits rotavirus replication and upregulates AQP4 expression in rotavirusinfected Caco-2 cells

Antiviral activities of resveratrol against rotavirus in vitro and in vivo

Inhibition effect of shengma-gegen-tang on measles virus in Vero cells and human peripheral blood mononuclear cells

Anti-viral effect of a compound isolated from Liriope platyphylla against hepatitis B virus in vitro

Antiviral biflavonoids from Radix Wikstroemiae (Liaogewanggen). Chinese Medicine

Anti-viral effect of a compound isolated from Liriope platyphylla against hepatitis B virus in vitro

Houttuynia cordata targets the beginning stage of herpes simplex virus infection

Immunomodulatory and antioxidant activities of fresh juice extracts of Brahmi and Guduchi

Expanding the activity spectrum of antiviral agents

Effects of virologic response to treatment on short-and long-term outcomes of patients with chronic hepatitis B virus infection and decompensated cirrhosis

Effect of coadministration of Hypoxis hemerocallidea extract and antiretroviral therapy (HAART) on the histomorphology and seminal parameters in Sprague Dawley rats

Homoisoflavonoids from Caesalpinia sappan displaying viral neuraminidases inhibition

Anti-HBV active constituents from Piper longum

Inhibitory effect of Phyllanthus urinaria L. extract on the replication of lamivudine-resistant hepatitis B virus in vitro

Antiviral phytochemicals: An overview

Determination of antioxidant activity, phenolic contents and antiviral potential of methanol extract of Euphorbia spinidens Bornm (Euphorbiaceae)

Anti-HIV activity of extracts and compounds from marine algae

Antiviral activity of Alpinia katsumadai extracts against rotaviruses

In vitro anti-rotavirus activity of polyphenol compounds isolated from the roots of Glycyrrhiza uralensis

Natural bis-benzylisoquinoline alkaloids-tetrandrine, fangchinoline, and cepharanthine, inhibit human coronavirus OC43 infection of MRC-5 human lung cells

Curcumin inhibits hepatitis C virus replication via suppressing the Akt-SREBP-1 pathway

Phenolic phytochemical displaying SARS-CoV papain-like protease inhibition from the seeds of Psoralea corylifolia

Immunomodulatory effects of Curcuma longa L. extract in LP-BM5 murine leukemia viruses-induced murine acquired immune deficiency syndrome

Genipin inhibits rotavirus-induced diarrhea by suppressing viral replication and regulating inflammatory responses

Genetic and antigenic diversity of human rotaviruses: Potential impact on vaccination programs

An evaluation of the inhibitory effects against rotavirus infection of edible plant extracts

The immunostimulatory and antimicrobial property of two herbal decoctions used in the management of HIV/AIDS in Ghana

Screening of dengue virus antiviral activity of marine seaweeds by an in situ enzyme linked immunosorbent assay

Inhibition of HIV-1 replication by a tricyclic coumarin GUT-70 in acutely and chronically infected cells

Yatein from Chamaecyparis obtusa suppresses herpes simplex virustype 1 replication in HeLa cells by interruption the immediate-early gene expression

Samarangenin B from Limonium sinense suppress herpes simplex virus type1 replication in vero cells by regulation of viral macromolecular synthesis

Antiviral traditional medicines against herpes simplex virus (HSV-1), poliovirus, and measles virus in vitro and their therapeutic efficacies for HSV-1 infection in mice

Efficacy of traditional herbal medicines in combination with acyclovir against herpes simplex virus type 1 infection in vitro and in vivo

Hepatitis B therapy

In vitro antiviral activity of phlorotannins isolated from Ecklonia cava against porcine epidemic diarrhea coronavirus infection and hemagglutination

Medicinal plants used in traditional medicine in the centre east region of Burkina Faso

Immunomodulatory and anti-SARS activities of Houttuynia cordata

Chemical composition and anti-herpes simplex virus type 1 (HSV-1) activity of extracts from Cornus canadensis

Nutraceutical activators of AMPK/Sirt1 axis inhibit viral production and protect neurons from neurodegenerative events triggered during HSV-1 infection

New anti-HBV C-boivinopyranosyl flavones from Alternanthera philoxeroides

Research progress and clinical application of matrine type

Identification of natural compounds with antiviral activities against SARS-associated coronavirus

Antiviral activity and mode of action of caffeoylquinic acids from Schefflera heptaphylla (L)

Lariciresinol-4-O-β-D-glucopyranoside from the root of Isatis indigotica inhibits influenza A virus-induced proinflammatory response

Structure, function, and evolution of coronavirus spike proteins

Anti-herpes simplex virus type 1 activity of Houttuynoid A, a flavonoid from Houttuynia cordata Thunb

Hepatitis B: The virus and disease

Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds

Aloe-emodin is an interferon-inducing agent with antiviral activity against Japanese encephalitis virus and enterovirus 71

Hydrolyzable tannins (chebulagic acid and punicalagin) target viral glycoprotein-glycosaminogly can interactions to inhibit herpes simplex virus 1 entry and cell to cell spread

Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry

Anti-enterovirus 71 activity screening of Chinese herbs with anti-infection and inflammation activities

Antiviral activities of biflavonoids

Cranberry and grape juices affect tight junctionfunction and structural integrity of rotavirus-infected monkey kidney epithelial cell monolayers

Effect of pH on anti-rotavirus activity by comestible juices andproanthocyanidins in a cell-free assay system

Comparison of α-glucosyl hesperidin of citrus fruits andepigallocatechingallate of green tea on the loss of rotavirus infectivity in cell culture

Antiviral effects on bacteriophages and rotavirus by cranberry juice

Efficacy of Thai medicinal plant extracts against herpes simplex virus type 1 infection in vitro and in vivo

Molecular genesis of drug-resistant and vaccine-escape HBV mutants

Silymarin suppresses basal and stimulus-induced activation, exhaustion, differentiation, and inflammatory markers in primary human immune cells

Narasin, a novel antiviral compound that blocks dengue virus protein expression

Ethnopharmacology in overdrive: The remarkable anti-HIV activity of Artemisia annua

AntiHSV activity of Kuwanon X from mulberry leaves with genes expression inhibitory and HSV-1 induced NF-kB deactivated properties

Uncinoside A and B, two new antiviral chromone glycosides from Selaginella uncinata

Antiviral spirooliganones A and B with unprecedented skeletons from the roots of Illicium oligandrum

Antiviral screening of British Columbian medicinal plants

Detection of calicivirus genome in calves using Ni/E3 primers in Shahrekord area

Pharmacological studies of ten medicinal plants used for analgesic purposes in Congo Brazzaville

Intravenous silibinin monotherapy shows significant antiviral activity in HCV-infected patients in the peri-transplantation period

Antiviral potential of curcumin

a glucosidic indole-lignan conjugate from an aqueous extract of the Isatis indigotica roots

Spicebush. A Cherokee remedy for the measles

Griffithsin has antiviral activity against hepatitis C virus

New insights into antioxidant and antiviral activities of two wild medicinal plants: Achillea fragrantissima and Nitraria retusa

Phytochemical study and anti viral effect evaluation of methanolic extract with fractions of aerial parts of Euphorbia spinidens

Effect of Moringa oleifera Lam. leaf powder on the pharmacokinetics of nevirapine in HIV-infected adults: A one sequence cross-over study

Herpes simplex virus resistance to antiviral drugs

Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: A meta-analysis of observational studies

HIV/AIDS review

Modelling measles re-emergence as a result of waning of immunity in vaccinated populations

Mortality by cause for eight regions of the world: Global Burden of Disease Study

Inhibition of rotavirus and enterovirus infections by tea extracts

Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona-and picornaviruses

Effect of pine seed shell extract on rotavirus and enterovirus infections

Effects of alkaloidal extract of Phyllanthus nirurion HIV replication

Inhibitory Activity of Avicennia marina, a Medicinal Plant in Persian Folk Medicine, against HIV and HSV

A structural analysis of M protein in coronavirus assembly and morphology

Successful prevention of hepatitis C virus (HCV) liver graft reinfection by silibinin mono-therapy

Hepatitis B vaccination in children: The Taiwan experience

A new class of DNA glycosylase/apurinic/apyrimidinic lyases that act on specific adenines in single stranded DNA

Editorial: Drug repositioning: Current advances and future perspectives

Antiviral activity of crude Hydroethanolic extract from Schinus terebinthifolia against herpes simplex virus type 1

In vivo evaluation of the antiviral activity of Cajanus cajan on measles virus

UPLC-PDA-ESI-qTOF-MS profiling and potent anti-HSV-II activity of Eucalyptus sideroxylon leaves

Antiviral activity of chilean medicinal plant extracts

Rotavirus and severe childhood diarrhea

Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event

Tanshinones as selective and slow-binding inhibitors for SARS-CoV cysteine proteases

Evaluation of polyphenols from Broussonetia papyrifera as coronavirus protease inhibitors

Traditional dietary additives of the Maasai are antiviral against the measles virus

Topical carbenoxolone sodium in the management of herpes simplex infection

Specific inhibition of human immunodeficiency virus type 1 reverse transcriptase mediated by soulattrolide, a coumarin isolated from the latex of Calophyllum teysmannii

Bioassay-guided isolation of anti-hepatitis B virus flavonoid myricetin-3-O-rhamnoside along with quercetin from Guiera senegalensis leaves

Therapeutic effect of meliacine, an antiviral derived from Melia azedarach L., in mice genital herpetic infection

RIG-I-mediated antiviral responses to single-stranded RNA bearing 5 0 -phosphates

Antiviral activity of the Lippia graveolens (Mexican oregano) essential oil and its main compound carvacrol against human and animal viruses

Response to the AIDS pandemic: A global health model

Drug repurposing approaches for the treatment of influenza viral infection: Reviving old drugs to fight against a long-lived enemy

Overview of influenza viruses

Identification of hepatoprotective flavonolignans from silymarin

Inhibition of T-cell inflammatory cytokines, hepatocyte NF-kappaB signaling, and HCV infection by standardized Silymarin

A review of the antiviral properties of Black elder (Sambucus nigra L.) products

Drug repurposing: Progress, challenges and recommendations

Anti-HBV agents derived from botanical origin

Antiviral action and selectivity of 6-azauridine

Deguanylation of human immunodeficiency virus (HIV-1) RNA by recombinant pokeweed antiviral protein

Antiviral effect of compounds derived from Angelica archangelica L. on herpes simplex virus-1 and Coxsackievirus B3 infections

Systemic rotavirus infection

Potent in vitro antiviral activity of Cistus incanus extract against HIV and Filoviruses targets viral envelope proteins

Curcumin inhibits hepatitis B virus via down-regulation of the metabolic coactivator PGC-1alpha

Anti-hepatitis C virus activity and synergistic effect of Nymphaea alba extracts and bioactive constituents in liver infected cells

Antiviral activity of Rhus aromatica (fragrant sumac) extract against two types of herpes simplex viruses in cell culture

Clinical review: Primary influenza viral pneumonia

Antiviral activity of a Arisaema tortuosum leaf extract and some of its constituents against herpes simplex virus type 2

Systemic features of rotavirus infection

A facile inhibitor screening of SARS coronavirus N protein using nanoparticle-based RNA oligonucleotide

Antiviral activity obtained from aqueous extracts of the Chilean soapbark tree (Quillaja saponaria Molina)

Prevention of rotavirus infections in vitro with aqueous extracts of Quillaja saponaria Molina

Elderberry flavonoids bind to and prevent H1N1 infection in vitro

Screening of antiviral activities in medicinal plants extracts against denguevirus using dengue NS2B-NS3 protease assay

Biflavonoids from Torreya nucifera displaying SARS-CoV 3CL pro inhibition

Measles: Not just a childhood rash

Antiviral lead compounds from marine sponges

Review of dengue hemorrhagic fever fatal cases seen among adults: A retrospective study

Influenza virus resistance to neuraminidase inhibitors

Reviewing the history of pandemic influenza: Understanding patterns of emergence and transmission

Evaluation of antirotavirus activity of flavonoids

Anti-HIV activity of extracts and compounds from algae and cyanobacteria

Apparently new enterovirus isolated from patients with disease of the central nervous system

Phylogenetic quantification of intra-tumour heterogeneity

Nordihydroguaiaretic acid (NDGA) inhibits replication and viral morphogenesis of dengue virus

Coronavirus envelope protein: Current knowledge

The antiviral agents, MAP30 and GAP31, are not toxic to human spermatozoa and may be useful in preventing the sexual transmission of human immunodeficiency virus type 1

In vitro effect of Dodonaea viscosa extracts on the replication of coxackievirus B3 (Nancy) and rotavirus (SA-11)

Evolution of Influenza a virus by mutation and re-assortment

HIV transmission. Cold Spring Harbor Perspectives in Medicine

Natural products that reduce rotavirus infectivity identified by a cell-based moderate-throughput screening assay

High-throughput screening and identification of potent broadspectrum inhibitors of coronaviruses

Anti-influenza virus activity of extracts from the stems of Jatropha multifida Linn

Broadspectrum antiviral activity of Virazole: 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide

Basics of the virology of HIV-1 and its replication

Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13

Recent advances in anti-HIV natural products

Mechanisms of inhibition of HIV replication by nonnucleoside reverse transcriptase inhibitors

Antiviral activity of Hederasaponin B from Hedera helix against enterovirus 71 subgenotypes C3 and C4a. Biomolecules and Therapeutics

Complete sequence analysis and antiviral screening of medicinal plants for human coxsackievirus a16 isolated in Korea

In vitro screening of anti HBV and anti HIV properties of Gymnema sylvestre R.Br leaves from Kolli Hills, Tamilnadu, India

Scientific barriers to developing vaccines against avian influenza viruses

Hepatitis C virus hijacks host lipid metabolism

In vitro antirotaviral activity of Achillea kellalensis

Antiviral lectins from red and blue-green algae show potent in vitro and in vivo activity against hepatitis C virus

Analysis of anti-rotavirus activity of extract from Stevia rebaudiana

Characterization of in vivo anti-rotavirus activities of saponin extracts from Quillaja saponaria Molina

Picornavirus and enterovirus diversity with associated human diseases

vitro antiviral activity against rotavirus and astrovirus infection exerted by substances obtained from Achyrocline bogotensis

Compositae)

EPs (R) 7630 (Umckaloabo (R)), an extract from Pelargonium sidoides roots, exerts anti-influenza virus activity in vitro and in vivo

Elderberry Supplementation Reduces Cold Duration and Symptoms in Air-Travellers: A Randomized, Double-Blind Placebo-Controlled Clinical Trial

In vitro inactivation of HBsAg by Eclipta alba Hassk and Phyllanthus niruri Linn

Ursolic acid: A novel antiviral compound inhibiting rotavirus infection in vitro

Bioactive constituents of Lindernia crustacea and its anti-EBV effect via Rta expression inhibition in the viral lytic cycle

Structural basis of SARS-CoV-2 3CL pro and anti-COVID-19 drug discovery from medicinal plants

Anthemis hyalina (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes family

Inactivation of pathogenic viruses by plant-derived tannins: strong effects of extracts from persimmon (Diospyros kaki) on a broad range of viruses

An evidence-based systematic review of elderberry and elderflower (Sambucus nigra) by the natural standard research collaboration

Human coronaviruses: What do they cause?

Antiviral compounds of natural origin

Effects of an extract from Phyllanthus nirurion hepatitis B and woodchuck hepatitis viruses: in vitro and in vivo studies

Chemical analysis and in vitro antiviral and antifungal activities of essential oils from Glechon spathulata and Glechon marifolia

Marine organisms as a therapeutic source against herpes simplex virus infection

Glycyrrhizic acid as the antiviral component of Glycyrrhiza uralensis Fisch. against coxsackievirus A16 and enterovirus 71 of hand foot and mouth disease

Herbs of the genus Phyllanthusin the treatment of chronic hepatitis B: Observations with three preparations from different geographic sites

Pokeweed antiviral protein cleaves double-stranded supercoiled DNA using the same active site required to depurinate rRNA

Reemerging of enterovirus 71 in Taiwan: The age impact on disease severity

In vitro activity of Paris polyphylla smith against enterovirus 71 and Coxsackievirus B3 and its immune modulation

Sheng-Ma-Ge-Gen-Tang (Shoma-kakkon-to) inhibited cytopathic effect of human respiratory syncytial virus in cell lines of human respiratory tract

Cimicifuga foetida L. inhibited human respiratory syncytial virus in HEp-2 and A549 cell lines

Antiviral effect of cimicifugin from Cimicifuga foetida against human respiratory syncytial virus

Flavone C-glycosides from the leaves of Lophatherum gracile and their in vitro antiviral activity

Reemerging of enterovirus 71 in Taiwan: The age impact on disease severity

Flavone C-glycosides from the leaves of Lophatherum gracile and their in vitro antiviral activity

New strategy for identifying potential natural HIV-1 non-nucleoside reverse transcriptase inhibitors against drugresistance: An in silico study

Antiviral activity of a polysaccharide from Radix Isatidis (Isatis indigotica Fortune) against hepatitis B virus (HBV) in vitro via activation of JAK/STAT signal pathway

Targeting human immunodeficiency virus type 1 assembly, maturation and budding

Effect of alcohol extract of Acanthus ilicifolius L. on anti-duck hepatitis B virus and protection of liver

New direct acting antiviral agents for the treatment of hepatitis C virus infection and perspectives

Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus

Traditional Chinese medicine herbal extracts of Cibotium barometz, Gentiana scabra, Dioscorea batatas, Cassia tora, and Taxillus chinensis inhibit SARS-CoV replication

Pneumonia of unknown cause -China, Emergencies preparedness, response. Disease Outbreak News

Human immunodeficiency virus and herbal medicine. Alternative and Complementary Therapies

Consumption of Sutherlandia frutescens by HIV-seropositive South African adults: An adaptive double-blind randomized placebo controlled trial

Small molecules targeting severe acute respiratory syndrome human coronavirus

Naturally derived anti-hepatitis B virus agents and their mechanism of action

The inhibitory effect of Rheum palmatum against coxsackievirus B3 in vitro and in vivo

Antiviral activity of polymethoxylated flavones from Guangchenpi, the edible and medicinal pericarps of Citrus reticulate 'Chachi'

Anti-HIV lignans from Justicia procumbens

Anti-hepatitis B virus activity of swertisin isolated from Iris tectorum Maxim

Hippomanin A from acetone extract of Phyllanthus urinaria inhibited HSV-2 but not HSV-1 infection in vitro

Identification of phenanthroindolizines and phenanthroquinolizidines as novel potent anti-coronaviral agents for porcine enteropathogenic coronavirus transmissible gastroenteritis virus and human severe acute respiratory syndrome coronavirus

Antiviral effect of geraniin on human enterovirus 71 in vitro and in vivo

Chebulagic acid, a hydrolyzable tannin, exhibited antiviral activity in vitro and in vivo against human enterovirus 71

Targeting coronaviral replication and cellular JAK2 mediated dominant NF-κB activation for comprehensive and ultimate inhibition of coronaviral activity

Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis

Total saponins extracted from Abrus cantoniensis Hance suppress hepatitis B virus replication in vitro and in rAAV8-1.3HBV transfected mice

Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells

Phytochemical profiling and antiviral activity of Ajuga bracteosa, Ajuga parviflora, Berberis lycium and Citrus lemon against Hepatitis C Virus

Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13

A inhibits dengue viral replication via upregulating antiviral interferon responses through STAT signaling pathway

Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections

Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L) during an outbreak of influenza B Panama

The pathogenesis of influenza in humans

Antiviral activity of four types of bioflavonoid against dengue virus type-2

Novel antiviral activity of baicalein against dengue virus

Re-emergence of measles among young adults in Marseilles

Resveratrol-mediated gamma interferon reduction prevents airway inflammation and airway hyper responsiveness in respiratory syncytial virusinfected immunocompromised mice

Anti-hepatitis B virus effects of dehydrocheilanthifoline from Corydalis saxicola

Naturally occurring and synthetic bioactive molecules as novel non-nucleoside HBV inhibitors

Contemporary clinical research of traditional Chinese medicines for chronic hepatitis B in China: An analytical review

Potent Inhibitor of Drug-Resistant HIV-1 Strains Identified from the Medicinal Plant Justicia gendarussa

Anti-HIV diphyllin glycosides from Justicia gendarussa

Drug repurposing screens and synergistic drugcombinations for infectious diseases

Anti-HIV-1 activity of trichobitacin, a novel ribosome inactivating protein

TLR3 deficiency in patients with herpes simplex encephalitis

Aurantiamide acetate from Baphicacanthus cusia root exhibits antiinflammatory and anti-viral effects via inhibition of the NF-κB signaling pathway in Influenza A virus-infected cells

Marine natural products with anti-HIV activities in the last decade

Inhibition of enterovirus 71 replication by chrysosplenetin and penduletin

Procyanidins and butanol extract of cinnamomi cortex inhibit SARS-CoV infection

Medicinal plants: Treasure for antiviral drug discovery