key: cord-309138-44qpk2vf
authors: Khanna, Kanika; Kohli, Sukhmeen Kaur; Kaur, Ravdeep; Bhardwaj, Abhay; Bhardwaj, Vinay; Ohri, Puja; Sharma, Anket; Ahmad, Ajaz; Bhardwaj, Renu; Ahmad, Parvaiz
title: Herbal Immune-boosters: Substantial Warriors of Pandemic Covid-19 Battle
date: 2020-10-03
journal: Phytomedicine
DOI: 10.1016/j.phymed.2020.153361
sha: 
doc_id: 309138
cord_uid: 44qpk2vf

Current scenario depicts that world has been clenched by COVID-19 pandemic. Inevitably, public health and safety measures could be undertaken in order to dwindle the infection threat and mortality. Moreover, to overcome the global menace and drawing out world from moribund stage, there is an exigency for social distancing and quarantines. Since December, 2019, coronavirus, SARS-CoV-2 (COVID-19) have came into existence and up till now world is still in the state of shock.At this point of time, COVID-19 has entered perilous phase, creating havoc among individuals, and this has been directly implied due to enhanced globalisation and ability of the virus to acclimatize at all conditions. The unabated transmission is due to lack of drugs, vaccines and therapeutics against this viral outbreak. But research is still underway to formulate the vaccines or drugs by this means, as scientific communities are continuously working to unravel the pharmacologically active compounds that might offer a new insight for curbing infections and pandemics. Therefore, the topical COVID-19 situation highlights an immediate need for effective therapeutics against SARS-CoV-2. Towards this effort, the present review discusses the vital concepts related to COVID-19, in terms of its origin, transmission, clinical aspects and diagnosis. However, here, we have formulated the novel concept hitherto, ancient means of traditional medicines or herbal plants to beat this pandemic.

Pandemic diseases are of global concern in the present era, to cause gigantic morbidity and transience, regardless of, extensive medical facilities. Particularly, anti-viral therapies have been fraught because of surfacing of mutants competent enough to subdue the drugs targeting disease that has created panic all over. By this review, we suggest that herbal or medicinal plant formulations could be essential alternative strategy, a step ahead to battle these awful viruses. Zhang and Holmes, 2020). Moreover, SARS-CoV-2 just like SARS-CoV utilizes the same ACE2 receptors to infect its hosts (Guo et al., 2020) . Thus, the sites where ACE2 protein is mainly expressed are the potential target sites for SARS-CoV-2 respectively. These regions are belong to type II alveolar cells of the lungs and enterocytes of the small intestine (Hamming et al., 2004; Zheng, 2020) . Nevertheless, there are some remarkable biological differences between the SARS-CoV-2 and the other beta-CoVs, which probably make it more infectious. Consequently, the epidemiological dynamics of SARS-CoV-2 is different from previous human-CoV outbreaks having striking local and global spread (Zhang and Holmes, 2020; Zheng, 2020).

Although, SARS-CoV-2 shows greater human-to-human transmission efficiency, its crude fatality rate (0.25% to 5%) is comparatively far less than that of SARS-CoV which is approx. 10%. Furthermore, SARS-CoV-2 has R 0 (basic reproduction number) of 4.7 to 6.6. This highly contagious nature of SARS-CoV-2 is supported by the fact that its spike (S) protein possess 10 to 20 time's greater affinity for ACE2 receptors than SARS-CoV (Zheng, 2020) . S-protein is the surface glycoprotein that assists the virus in the attachment to the host cells through its receptor-binding domain (RBD). S-protein has several domains, one of the sections termed as ectodomain has two subunits, S1 and S2, which form a crown-like structure around the virus (Vellingiri et al., 2020) . Besides, S-protein of SARS-CoV-2 contains a furin-like cleavage site at the S1-S2 junction, missing in other members of its sister clade. This additional cleavage site might also be responsible for greater pathogenicity of SARS-CoV-2 as it also occurs in highly infectious form of influenza virus but lacking in less pathogenic ones (Coutard et al., 2020; Zhang and Holmes, 2020).3. Origin and

The natural reservoir for both the SARS-CoV and MERS-CoV were bats; however, these viruses infect humans through an intermediate host. Palm civets are supposed to be the intermediate host of SARS-CoV while dromedary camels are of MERS-CoV (Yin and Wunderink, 2018) .Unfortunately, the exact zoonotic origin of SARS-CoV-2 is still elusive.

Since SARS-CoV-2 shares 88% nucleotide homology with two SARS-like CoV found in bats (bat-SL-CoVZC45 and bat-SL-CoVZXC21) and 96% with RaTG13 virus found in horseshoe bat (Rhinolophus affinis), bats are considered to be its natural host (Lu et al., 2020b; Zhou et al., 2020b) . Despite the 96% nucleotide similarity, the RBD of both the viruses varies significantly (Mackenzie and Smith, 2020) . However, due to the ecological separation of the bats from the humans and the requirement of some necessary mutations in the virus genome to cross the species barrier, SARS-CoV-2 likely has one or more mammalian intermediate hosts for efficient animal-to-human transmission (Zhang and Holmes, 2020) . Analyses of interactions between RBD in SARS-CoV-2 and ACE2 receptors in different hosts indicate that pangolins, snakes, and turtles may be the immediate host of SARS-CoV-2 (Liu et al., 2020) (Fig. 1) . Recent phylogenetic studies on the genome of Pangolin-CoV found from dead Malayan pangolins, which are illegally imported in China revealed that its genome is about 91% identical to SARS-CoV-2 and around 90% to RaTG13 (Bat-CoV). Besides, five of the six amino acids (contact residues) on RBD, vital for binding to ACE2 receptors on hosts are consistent between SARS-CoV-2 and Pangolin-CoV, but only four between Pangolin-CoV and RaTG13 and only one out of six between SARS-CoV and SARS-CoV-2 (Zhang et al., 

Person-to-person transmission is primarily reported in families, communities, and hospitals (Guo et al., 2020) . Droplet transmission is considered as the main route of person-to-person transmission (Han et al., 2020) . The infection also spreads through direct contact and via fomite exposure i.e., direct contact to eyes, nose, and mouth after touching surfaces and objects contaminated by an infected individual Morawskaa and Cao, 2020) . In general, human-CoVs can remain infectious on some material surfaces for even 9 days (Kampf et al., 2020) . Besides, SARS-CoV-2 also spreads through contact with asymptomatic carriers . Since SARS-CoV-2 infection is spreading at an unprecedented pace, airborne transmission too warrants meticulous determination (Morawskaa and Cao, 2020). In addition, SARS-CoV-2 was found in a stool sample, gastrointestinal tissue even urine and saliva of an infected person, suggests the possibility of intestinal and fecal-oral transmission (Xiao et al., 2020; Guan et al., 2020) . Although no case of mother to child transmission has been reported yet, infection in two newborns of Wuhan, China raises the question for vertical transmission (Han et al., 2020) . Apart from this, there are recent studies that reveal that there is a possibility of sexual transmission of COVID-19

infection. There are an array of evidences for this transmission such as through faecal-oral route via gastrointestinal infection . This is most probably due to ACE2 that enable virus entry and ACE2 mRNA is overexpressed in gastro-intestinal system as revealed through immunofluorescent analysis of rectal epithelial cells (Hindson, 2020).

Moreover, RNA analysis of SARS-CoV-2 also revealed that the viral particles can infect these cells therefore, it is quite predictable that sexual intercourse could be the possible way of contagion. There have been cases when person shows negative results on nasopharyngeal swabs, while, positive on rectal swabs, depicting that sexual transmission might be the possibility . Henceforth, the physicians as well as doctors in particular recommend a strong message to discourage sexual practices if in any case of COVID-19 infection. Hence, comprehensive possible means of SARS-CoV-2 transmission warrants further study.

suggests this novel SARS-CoV-2 affects elderly people with coexisting other medical complications more seriously. These results are consistent with previous studies conducted on severely ill patients which also advocates high mortality rate in elderly people with acute respiratory distress syndrome (ARDS) and comorbidities such as hypertension, diabetes, chronic obstructive lung disease and coronary heart disease Zhou et al., 2020a) . The most common complications associated with SARS-CoV-2 infection are sepsis, respiratory and heart failure, ARDS, and septic shock (Zhou et al., 2020a) . Even though children of all ages face risk of SARS-CoV infection, the serious progression of infection and morbidity is rare in children and adolescents relative to the adults (Lu et al., 2020a).

SARS-CoV-2 infection is often categorized into three stages: first, asymptomatic phase; second, non-severe symptomatic phase; and third, severe respiratory symptomatic phase (Shi et al., 2020) . Usually, a small number of patient's progress to the severe stage and develop ARDS and/or multiorgan failure (Cao et al., 2020).

Host's immune responses initiate as soon as SARS-CoV-2 binds to ACE2 receptors and releases viral RNA for replication. Both the innate and adaptive immune response could be triggered in response to the SARS-CoV-2 infection (Cao et al., 2020). However, immune responses are different between severely and moderately infected persons. In a blood sample of symptomatic hospitalised patients with mild to moderate SARS-CoV-2 infection before resolution of symptoms, immunological changes such as increase in the number of activated CD4+ helper T cells and CD8+ killer T cells, follicular helper T (Tfh) cells, antibodysecreting cells (ASCs) and antibodies particularly IgG (Immunoglobulin G)and IgM (Immunoglobulin M) were detected (Thevarajan, 2020) . On the other hand, in severely infected patients, lymphocytopenia is a common denominator with substantial fall in numbers of natural killer cells, B cells, CD3+ T cells, CD4+ helper T cells, CD8+ killer T cells along with the increase in neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein levels.

Additionally, in comparison to the non-severe patients, pro-inflammatory cytokines and chemokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, Granulocyte-colony stimulating factor (GCSF), monocytechemoattractant protein 1 (MCP1) and macrophage inflammatory protein 1-alpha (MIP1-alpha) are often reported to be elevated in serum levels of critically ill patients (Huang et al., 2020; Qin et al., 2020; Wang et al., 2020a) . The elevated ratio of NLR, which is a biomarker of systemic inflammatory response syndrome, points to the devastated inflammatory state of ICU patients (Salciccioli et al., 2015) . Moreover, uncontrolled levels of cytokines and chemokines cause over-active inflammatory responses or cytokine storm. This hyperactive immune response along with impaired adaptive immune response may trigger pulmonary injury, ARDS, viral sepsis and organ failure like complications, and eventually death in some cases (Prompetchara et al., 2020) .

The traditional Chinese medicines and Ayurveda since the Vedic period (1500-500 BCE) provides globally with potential remedies to lessen the severity of the illnesses caused by 

The traditional medicines have been in general disregarded in the novel research and expansion of contemporary drugs due to the fact that their translational ability is commonly i.e. curumin, is identified to block cytokine release, specifically interleukin-1, interleukin-6, pro-inflammatory cytokines and tumor necrosis factor-α and is directed to be consumed with milk (Omara et al., 2010) . Inhibition of the cytokine discharge is one of the prime clinical development associated with experimental modules of flu and other infectious diseases and have also been compared to COVID-19 where similar cytokine storm play an imperative role in transience (Sordillo et al., 2015) . Moreover, AYUSH has recommended certain preventive and medicinal plants for prevention and prophylactic of COVID-19 including warm extracts of Tinospora cordifolia (advised for chronic fever), Andrograhis paniculata (advised for fever and cold), Cydonia oblonga, Zizyphus jujube and Cordia myxa (enhancing antioxidant, immune-modulatory, anti-allergic, smooth muscle relaxant, anti-influenza activity) and

Arsenicum album 30 (found effective against SARS-CoV-2, immune-modulator). The symptomatic management of COVID-19 was suggested to be acquired from Agastya Haritaki 

The polysaccharides are a structurally multifaceted class of biomolecules that have diverse Therefore, these biocompatible compounds were suggested to be employed in coating materials of various sanitary items for COVID-19 deterrence.

The naturally occurring products and phytomedicines are coming to the fore all around the (Sengupta, 2020 ). According to their study, 'Aurantiamide', an active metabolite from Piper aurantiacum has chymotrypsin like-proteases like activities that is a ratified agent for inhibiting coronavirus. In addition to this, it also encompassespiperol, eugenol, catechol, caryophyllene, etragol, chavibetol, betlol, quercetin etc. that also grows body's self-defense mechanism either through reception of viruses or in waning off the viral load within the infected hosts (Sengupta, 2020) .Alongside, studies have been depicted the role of herbal drug Gene-Eden-VIR/Novirin against many noxious viruses and this drug is mainly comprised of quercetin, green tea, cinnamon, licorice and selenium (Polansky and Lori, 2020). They found that it disrupts the viral entry, infection, replication, viral proteases, viral quasi-speciesand triggers the immunity, thereby, can be evidently utilised against SARS-CoV-2 respectively (Polansky and Lori, 2020).

Interestingly, the role of tulsi for scientific evidence against COVID-19 has also been elucidated (Goothy et al., 2020). As, it is well known herbal plant for antiviral effects in inhibiting many deadly viruses like vaccinia, dengue, hepatitis, encephalitis etc. by enhancing their survival and defense ability. Moreover, it also reinstate the physiological functions of body through its phenolic and antioxidative property that in turns shields the body from toxic substances (Shivananjappa and Joshi, 2012) . The most possible mechanism underlying its immunity boosters lies in triggering humoral and cellular immunity responses (Vaghasiya et al., 2010) . Apart from this, modulatory actions of GABA pathway also encompass their multi-modal therapeutic properties, therefore, we can conjecture that it could be efficient in cure of COVID-19. Nevertheless, the role of Persian herbs have also been untangled against 

Coronavirus COVID-19 pandemic is a huge catastrophe that has caused devastating effects However, the biological activities can also be improved by ingesting high levels of naturally existing polyphenols that not only elicit immunity against viruses but they are also comprised of receptors that identifies and permit their cellular uptake for activating signaling cascade are also hindered by smoke.Therefore, these steps can reboot the immune system and reinforce the inner forces to battle against severe viral infections COVID-19 respectively.

The most momentous weapon against any kind of viral infection is a strong immune system. 

Vitamin A is an essential fat-soluble vitamin which has a major involvement in regulating vision, growth and maturity as well as protection of the mucosal and epithelium had the highest inhibitory potential against SARS-CoV-2, followed by galangal, sappan wood and curcuma species and it was further suggested that they might have antiviral potency against COVID-19. Additionally, different plant based sources of vitamins include, mushrooms, carrots, broccoli, almonds, citrus, guava, amla, avocados etc. Fig. 3 describes the role of Vitamins (A, C, E and D) in combating COVID-19.

Zinc is one of the indispensible elements which has significant role in modulation of growth and development and the regulation of the immunomodulatory responses In addition to this, another trace element that has been reported to have wide range of pleiotropic effects ranges from anti-inflammatory to antioxidative is Selenium (Se) (Rayman, 2012) . Comparatively, the lower concentrations of Se are related to enhancement in the jeopardy of mortality, meager immune responses and cognitive reduction, whereas the higher doses are affirmed to show antiviral activity (Rayman, 2012) . Supplementation of Se results in elevation in concentration of Se in the plasma, up-regulation of lymphocyte phospholipid levels and activity of GPOX in the cell, subsequently leading elevation in cellular immune response. The humoral response was shown to be un-affected (Broome et al., 2004) . Similar reports of hasty clearance of poliovirus were also reported by Se supplementation (Ivory et al., 2017). Various plants namely, beans, nuts, peanuts, grains, mushrooms, cereals, lentils, garlic, grains, etc. have been wide sources of minerals and must be included in diet.

Nutraceuticals are the products which are argued to provide physiological assistance and protection against varied persistent diseases. Wide range of nutraceutical products have been isolated herbal products, dietary supplements, isolated nutrients, genetically engineered foods and processed cereals, beverages and soups (Kalra, 2003) . Certain nutraceuticals have been shown earlier to enhance the immune function. McCarty and DiNicolantonio (2020) elucidated that, a few nutraceuticals were able to lower the degree of symptoms and provide respite to the patients infected from coronavirus and influenza. Another significant product is probiotic, they are defined as live micro-organisms which bestow varied health benefits such as improvement in gastrointestinal activity (Sanders, 2008) . They also induce certain specific immune responses by augmenting antibody synthesis (Kanauchi et al., 2018) . A report by 

PAKs belong to mammalian kinases family also known as RAC/CDC42-activated kinases that have been came into existence since decades. Amid, these classes PAK1 is most prominent category of "pathogenic kinases" that can cause a plethora of diseases like cancer, inflammation, malaria, dengue, immuno-suppression and many antiviral diseases, if behave abnormally (Maruta, 2020) . Strikingly, PAK1-blockers (naturally existing) such as caffeic acid, its esters, bee-product propolis have been observed to inhibit RAC that directly activates PAK1 (Xu et al., 2005) . However, previous studies reported that chloroquine a drug active against malaria also suppressed the incidence of SARS/Coronavirus infection, but its mode of action still remains unknown (Vinecent, 2005) . Later, it was reported that this drug induced CDK inhibitor (p21) to inhibit PAK1 activity (Maruta, 2014) . In line of forging argument, a recent study depicted that tumor-repressed phosphatase PTEN, mainly involved in impeding PAK1 also inhibited the coronavirus-curbed LLC2-linked fibrosis (Lu, 2020). Moreover, LLC2 expression has been observed to correlate with ACE2, a coronavirus receptor and CK2/RAS-PAK1-AP1 signaling cascade (Chen et al., 2010) . Henceforth, through all these assumptions we can deduce the PAK1-reliance of corona pathogenesis and a suggestion of using PAK1-blockers for treating pandemic COVID-19 outbreak (Fig. 4) Inevitably, the conventional and recently accepted product propolis, obtained from bees have been known since ancient times. It is formerly obtained from honey-bee extract via honey-bees feeding the buds of poplar and willow trees, thereby, mixing their saliva into it to form hexagonal bee-hives in order to protect their larval species against many pathogenic organisms. This product synthesised is called as propolis and is regarded as herbal medicine with anti-viral properties. In contemporary world, propolis is identified in possessing anticancer characteristics due to the presence of an ingredient CAPE (Caffeic Acid Phenyl Ester) involved in down-regulation of RAC for PAK1 inhibition respectively (Xu et al., 2005) .

Although, the anticancer constituents in propolis varies from product to product according to harvesting property of bee extracts. For instance, the anti-cancer element in Brazilian propolis is Artepillin C (ARC), while in sub-tropical regions of Taiwan and Okinawa, polyphenols namely, Nymphaeols act as direct inhibitors of PAK1 .In view of the fact that, familiar thing among all categories is that they are comprised of PAK1-blockers.

Ever since, has been elucidated that, PAK1 tends to cause cancers, viral diseases like HIV, Hepatitis, pappiloma, influenza, ebola, SARS and corona virus along with immune system suppression of hosts, henceforth, propolis would be quintessential in blocking COVID/coronavirus curbed fibrosis in respiratory tract and boosting the immunity of an individual (Maruta, 2014) . The effectiveness of propolis also depends on the product, its chemical nature and action. To expedite, CAPE-containing propolis named 'Bio 30', commercialised by New Zealand is found to be highly active (Maruta, 2014) . The optimal doses are 1 ml/10 Kg of the body weight. Regardless of this pre-formed formulation in the market, it could not be used against COVID-19 eruption, due to paucity of its stock in market place. Moreover, the available stocks are being predominantly used for treating patients with deadly cancers and prolonged treatment of genetic brain disorder, NF tumers (Neuro Fibromatosis Type 1, 2) (Maruta and He, 2020). In addition to this, the cell membrane permeability of caffeic acid and ARC is relatively weak, owing to its -COOH moiety.

Nonetheless, this feature could be surmounted by triggering the cell membrane permeability via conversion their esters into 1, 2, 3-triazolyl esters that are thousand times more powerful than ARC or caffeine esters (Maruta and Ahn, 2017) . Along with this, melatonin hormone (pineal gland hormone) is a serotonin and possess anti-melanogenic activity that is a primitive factor as melanogenesis is directly correlated to PAK1 . Further, it also owns similarity with other anti-PAK1 actions like anti-cancer, antiviral, antiinflammatory, immuno-boosters etc. Therefore, it is pertinent to mention here that melatonin, a commonly available sleeping pill could be utilized against coronaviral infections. Currently, many investigations are being carried out to high-light the significance of melatonin as another therapeutic resort or COVID-19 adjuvant (Zhang et al., 2020b) . Furthermore, glucocorticoid hormone 'ciclesonide' is another choice to cure different inflammatory disorders and it has been widely commercialised under the brand name of Alvesco. It has been officially approved since 1990 and been widely associated with treating adults as well as children. The molecular mechanism forming the basis for anti-inflammatory action is based on the potential of PAK1-blockers that lays the foundation for its pathway. Majorly, it works according to two basic reasons, firstly, inflammation is not possible without PAK1 and Apart from this, a herbal formulation mainly triterpenes or steroid named 'triptolide' derived from thunder god vine also inhibited RAC followed by blocking PAK1 route (Maruta and Ahn, 2017) . This medicine was previously treating the patients infected with dengue virus in restricting the proliferation of virus in lungs by blocking PAK1 signaling cascade (Liou et al., 2008) . Conversely, due to its lower water solubility, few years back, its -OH group was phosphorylated to enhance its solubility (Patil et al., 2015) . Resultantly, phosphotase-receptive pro-drug of triptolide 'Minnelide' is currently under clinical trials to cure COVID-19 infections as well. Another compound ivermectin has been screened from bacteria but with some lethal effects. Interestingly, these ill-effects were removed later by chemically re-designing the compound. (Hirokawa et al., 2005) . Therefore, possessing all these features it was approved to cure rare cancer disease cutaneous lymphoma and commercialised as 'Isodax' in market. However, research is being conducted with the belief that it could be most probably utilized for COVID-19 therapy. It is need of an hour to clinically test various PAK1-blockers against blocking virus replication to develop anti-COVID-19 therapy for patients suffering worldwide.

Strata of mankind has been marred with the onset of the unexpected pandemics, leading to the atrocious effects on their entire communities. Considering themselves invincible to conquer the world, they have now become the cocoons of their houses against COVID-19 storm. Unfortunately, SARS-CoV-2 has led the global population on their toes due to its highly infectious nature and susceptibility towards humans in causing higher mortalities among them. We can also introspect that about a lot many cases of COVID-19 have been undetected and by looking into the ongoing trends, the cases are doing to inflate in the coming future. This would ultimately affect the world economy, specifically within developing and under-developing nations. Besides, WHO has advised the world to take preventive measures, owing to which government has facilitated nationwide shutdowns, selfquarantine, physical distancing to ensure public safety. Thus far, the prevailing drugs and vaccines for antiviral diseases have been used as clinical trials to fight against coronavirus. 

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influencethe work reported in this paper. 

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Host Cell Copper Transporters CTR1 and ATP7A are important for Influenza A virus replication

The association between the neutrophil-to-lymphocyte ratio and mortality in critical illness: an observational cohort study

Probiotics: definition, sources, selection, and uses

Natural Immune Boosters as First-Line Armours to Combat Viral Infection-COVID19: Myth or Science?

Isolation and characterization of sulphated polysaccharides from Codium tomentosum (J. Stackhouse, 1797) collected from southeast coast of India

Use of Piper Betel to combat COVID19

Hispidin and Lepidine E: two Natural Compounds and Folic acid as Potential Inhibitors of 2019-novel coronavirus Main Protease (2019-nCoVMpro), molecular docking and SAR study

Molecular Docking study of novel COVID-19 Protease with low risk Terpenoides Compounds of Plants

Swine flu and its herbal remedies

Molecular docking studies on Jensenone from eucalyptus essential oil as a potential inhibitor of COVID 19 corona virus infection

Computational Drug Simulation: A step to the possible cure of COVID-19

COVID-19 infection: the perspectives on immune responses

Aqueous extract of tulsi (Ocimum sanctum) enhances endogenous antioxidant defenses of human hepatoma cell line (HepG2)

Plants as potential sources of natural immunomodulators

Activation of a PAK-MEK signalling pathway in malaria parasite-infected erythrocytes

The role of vitamin A in enhancing humoral immunity produced by antirabies vaccine

Antiviral effect of catechins in green tea on influenza virus

From SARS to MERS, thrusting coronaviruses into the spotlight

Curcumin suppression of cytokine release and cytokine storm. A potential therapy for patients with Ebola and other severe viral infections

On the Inhibition of COVID-19

Protease by Indian Herbal Plants: An In Silico Investigation

A novel anti-inflammatory natural product from Sphaeranthus indicus inhibits expression of VCAM1 and ICAM1, and slows atherosclerosis progression independent of lipid changes

The potential application of the traditional Chinese herb Exocarpium Citri grandis in the prevention and treatment of COVID-19

Basic principles of pharmaceutical science in Ayurvĕda

Antiviral and antioxidant activities of two medicinal plants

Traditional herbal drugs of Bulamogi, Uganda: plants, use and administration

Anti-viral activity of red microalgal polysaccharides against retroviruses

Black seed (Nigella sativa) and its constituent thymoquinone as an antidote or a protective agent against natural or chemical toxicities

Methanol and aqueous extracts of Ocimum kilimandscharicum (Karpuratulasi) inhibits HIV-1 reverse transcriptase in vitro

Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19

Betulinic acid: a new cytotoxic compound against malignant head and neck cancer cells

Investigation into SARS-CoV-2 Resistance of Compounds in Garlic Essential Oil

Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia

Antioxidant activity tests on novel triterpenoids from Salvia macrochlamys

Long-term high copper intake: effects on indexes of copper status, antioxidant status, and immune function in young men

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

Revealing the Potency of Citrus and Galangal Constituents to Halt SARS-CoV-2 Infection

Comparative evaluation of alcoholic and aqueous extracts of Ocimum sanctum for immunomodulatory activity

In vitro and in vivo Antiviral Potential of Hot Aqueous Extract of Ocimum sanctum and Argemone mexicana Leaves

COVID-19: A promising cure for the global panic

Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part I: Chemical diversity, impacts on plant biology and human health

Antivirals against animal viruses

Medicinal plants of Tamil Nadu (Southern India) are a rich source of antiviral activities

Chloroquine is a potent inhibitor of SARS coronavirus infection and spread

Effect of Nilavembu kudineer in the Prevention and Management of COVID-19 by inhibiting ACE2 Receptor

Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus

The laboratory tests and host immunity of COVID-19 patients with different severity of illness

Search of Preventative Strategies: Novel Anti-Inflammatory High-CBD Cannabis Sativa Extracts Modulate ACE2 Expression in COVID-19 Gateway Tissues

Anti-influenza agents from plants and traditional Chinese medicine

Adaptogens: Herbs for Strength. Stam. Stress Rel

Contribution of selected vitamins and trace elements to immune function

SituationReport-88. World Health Organization

WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems

Evidence for Gastrointestinal Infection of SARS-CoV-2

Downregulation of Rac1 activation by caffeic acid in aortic smooth muscle cells

Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

Traditional Chinese medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): a review and perspective

Herbs for Viral Respiratory Infections

Herbal extracts as antiviral agents

Water extract of licorice had anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines

MERS, SARS and other coronaviruses as causes of pneumonia

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

The traditional medicine and modern medicine from natural products

COVID-19: Melatonin as a potential adjuvant treatment

Probable pangolin origin of SARS-CoV-2 associated with the COVID-19 outbreak

A Genomic Perspective on the Origin and Emergence of SARS-CoV-2

SARS-CoV-2: An Emerging Coronavirus that Causes a Global Threat

Clinical course and risk factors for mortality of adult in patients with COVID-19 in Wuhan, China: a retrospective cohort study

A pneumonia outbreak associated with a new coronavirus of probable bat origin

None

List of Tables: Table 1 . Herbal Formulations as Possible Therapeutics against COVID-19 Infection

Mechanism of Action Therapeutic Property References

Anti-inflammatory action by via modulation of gene expression of ACE2 enzyme, serine protease TMPRSS2, protein pre-requisite for SARS-CoV2 invasion into host cells.Adjunct therapy and utilised as mouthwash and throat gargle products clinically and home use owing to their potential to decrease viral entry via the oral mucosa. 15.

Highest ACE2 enzyme inhibition, anti-inflammatory activity, modulated -gene expression for TNF-production in macrophages.Bioactive compounds could be used for drug formulations. 17.

Ginkgolic acids Impeded DNA and protein synthesis by binding towards host cell receptors to activate cellsignaling pathways for arresting cell cycle as an inhibitory action.