key: cord-0800541-gm5jffvo authors: Hasanzadeh, Akbar; Alamdaran, Masoomeh; Ahmadi, Sepideh; Nourizadeh, Helena; Bagherzadeh, Mohammad Aref; Jahromi, Mirza Ali Mofazzal; Simon, Perikles; Karimi, Mahdi; Hamblin, Michael R. title: Nanotechnology against COVID-19: Immunization, diagnostic and therapeutic studies date: 2021-06-25 journal: J Control Release DOI: 10.1016/j.jconrel.2021.06.036 sha: f57168efe3bab9d16c5d3c7f0ef7ab87d2c811ed doc_id: 800541 cord_uid: gm5jffvo The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in early 2020 soon led to the global pandemic of Coronavirus Disease 2019 (COVID-19). Since then, the clinical and scientific communities have been closely collaborating to develop effective strategies for controlling the ongoing pandemic. The game-changing fields of recent years, nanotechnology and nanomedicine have the potential to not only design new approaches, but also to improve existing methods for the fight against COVID-19. Nanomaterials can be used in the development of highly efficient, reusable personal protective equipment, and antiviral nano-coatings in public settings could prevent the spread of SARS-CoV-2. Smart nanocarriers have accelerated the design of several therapeutic, prophylactic, or immune-mediated approaches against COVID-19. Some nanovaccines have even entered Phase IΙ/IIΙ clinical trials. Several rapid and cost-effective COVID-19 diagnostic techniques have also been devised based on nanobiosensors, lab-on-a-chip systems, or nanopore technology. Here, we provide an overview of the emerging role of nanotechnology in the prevention, diagnosis, and treatment of COVID-19. In December 2019 the novel coronavirus (2019-nCoV), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, China. The virus belongs to the betacoronavirus family, and is the causative agent of Coronavirus Disease 2019 (COVID-19) (1, 2) . Due to its possible asymptomatic transmission, long incubation period, and its highly age-dependent infection fatality rate, SARS-CoV-2 is a In the past two centuries, the protective function of vaccination has saved innumerable lives in the battle against infectious and contagious diseases (29) . Today, amid growing concerns over the global threat of COVID-19, scientists have already developed some effective vaccine candidates, to contain the ongoing pandemic (30) . In an effort to further improve effectiveness of immunization and to provide safe alternatives to more traditional approaches, some nanotechnology-based vaccines have shown early promise against SARS-CoV-2. Nanovaccines have the potential to overcome some limitations of conventional immunization platforms (45, 46). Many nanosystems have been designed to prevent the premature degradation of subunit vaccines and enhance their targeted delivery. Mishra et al. employed HBsAg-functionalized solid lipid nanoparticles (SLNs) to deliver the surface antigen (HBsAg) to provide a subunit vaccine against hepatitis B virus. They showed that the HBsAg-functionalized SLNs had a higher cellular uptake, lower cellular toxicity, and greater induction of type 1 immune responses including CMI and AMI (47). Nanocarriers such as poly(lactic-co-glycolic acid) (PLGA), approved by the United States passed Phase IIΙ clinical trial with 89.3% efficiency (55, 56). Not only can NPs serve as delivery vehicles for antigens and adjuvants at the same time, but they can also act as stimulators of immune response due to their inherent adjuvanticity, thereby synergistically promoting an antigen-specific cellular immune response. In this regard, Sekimukai et al. prepared a vaccine adjuvant using gold NPs combined with the NALP3 inflammasome against SARS-CoV, which was capable of activating dendritic cells (DCs) in a similar manner to alum (aluminum hydroxide) used as the most common adjuvant (57) . Other nanoparticle-based vaccine adjuvants, such as metallic NPs, magnetic NPs, polymeric NPs, J o u r n a l P r e -p r o o f Journal Pre-proof dendrimers, and quantum dots may also have the potential to be used in both, prevention of infectious disease, and in cancer therapy (58) . The development of virus-like proteins (VLPs) has enabled the self-assembly of different genetically-engineered viral structural proteins with a diameter of 20-100 nm, which facilitates their uptake by DCs and macrophages. The use of VPLs can boost the weak immune response typical of subunit vaccines, while avoiding the risk of active infection caused by whole-virus vaccines due to their non-replicative property (59) . Using VLPs for inoculation allows for both robust AMI and CMI, and researchers formulated commercially available prophylactic VLP-based vaccines against both the hepatitis B virus (HBV) and human papillomavirus (HPV) (60) . Pushko et al. working at Novavax produced a trivalent seasonal influenza (H3N2, H1N1, and type B influenza) vaccine based on a VLP platform containing three hemagglutinin (HA) subtypes of H5N1, H7N2, and H2N3 influenza viruses (61) . Additionally, a large number of non-pathogenic VLP-based vaccines with strong AMI and CMI were designed to control MERS-CoVs and SARS-CoVs (62) (63) (64) (65) (66) . Currently, extensive research is underway to create a viable vaccine against the novel coronavirus relying on highly-ordered, stable, and monodisperse VLP-based vaccine formulations. For instance, Nicotiana benthamiana is being studied by some companies to develop genetically engineered VLP vaccines using the spike (S) protein of SARS-CoV-2. The vaccine candidates of Medicago and SpyBiotech (Serum Institute of India) have entered Phase Ι/ΙΙ and ΙΙ/IΙΙ clinical trials (35, 67), respectively. Genetic fragments that encode antigenic peptides or proteins can be delivered to indirectly induce an immune response against viral proteins (68) . These nucleic acid-based vaccines enjoy a range of benefits, including scalability, safety, and prolonged-expression of antigens (69) , thereby eliciting antigen-specific B cells, CD4 + T cells, and CD8 + cytotoxic T cells (70, 71) . However, there are some serious challenges regarding the delivery of gene-based vaccines, including low cellular uptake efficiency, several off-target effects, and low stability under physiological conditions (70, 72, 73) , which have led many clinical trials to failure University of Sydney, Bionet Co., Ltd. Technovalia (Australia) (83), and Takis/Rottapharm Biotech (Italy) (84) have developed DNA vaccine candidates for COVID-19, which are currently under different phases of clinical trials. All these DNA vaccines are administered using replacement delivery methods such as adjuvants, nanovehicles, etc. to avoid the low immunogenicity associated with the needle-injection of this vaccine type (35). Nanocarriers hold great promise in the delivery of vaccines to target specific cells and subcellular locations. Xu et al. synthesized surface-engineered gold nanorods to transfer the human immunodeficiency virus (HIV)-1 Env plasmid DNA for the immunization against HIV-1. The nanosystem was reported to stimulate good cellular and humoral immunity, coupled with T cell proliferation via APCs, compared to naked HIV-1 Env plasmid DNA (85) . Shim (88) . In another study, Zhang et al. With the aim of overcoming an aversion to vaccination, especially among children, approaches are being made to replace invasive administration routes including intramuscular and subcutaneous injections, with painless, non-invasive vaccination methods such as oral administration, inhalation, and microneedle injection. Recently, a growing number of nanovaccines have been designed to be administered by non-invasive routes (e.g., oral, nasal, J o u r n a l P r e -p r o o f diffusion nanopatches, or microneedle arrays) ( Figure 3 ) (98) (99) (100) . Mucosal nanovaccines have shown improved immune responses, with advantages of encapsulating security payloads for protection against degradation, targeting the mucosal immune system, and integrating a mucosal adjuvant with the vaccine preparation (101) . Nanotechnology has also allowed the oral delivery of VLPs, and intranasal delivery of viral vectors or proteasomes in clinical trials (46). For instance, gold NPs and alginate-coated chitosan NPs have been synthesized for the intranasal delivery of H1N1Me2 and HBsAg, respectively (102, 103) . Plant virus-derived NPs with good oral bioavailability and stability in the gastrointestinal tract have also been found suitable for oral immunization (104, 105) . Another drawback of conventional vaccines is the requirement for a booster dose, which may lessen patient compliance and acceptance even further. Thus, needle-free and pain-free nanopatches have been suggested to be a safe, effective, and self-administered vaccine delivery approach that could accelerate the dissemination of vaccines and ease the burden on healthcare systems (106, 107) . Furthermore, there have been some single-dose slow-release systems, including nanotechnology-based implants (108), thin-film-based vaccines, needle-free nanovaccines, and intranasal nanotechnology-based vaccines, which have been developed to overcome the challenges mentioned above (109, 110) . The worldwide distribution of conventional common vaccine formulations, such as solution-based vaccines, particularly in least-developed countries, is logistically difficult due to their need for constant refrigeration to preserve their efficacy. Hence, various types of long-term stable nanotechnology-based vaccines that do not require a cold-chain process have been created. For example, nanoscale building blocks derived from cowpea mosaic virus could act as stable nanocontainers with the ability to protect their cargo for over one hour at around 60°C, and indefinitely at ambient temperature (111) . Moreover, nanoemulsion vaccines with the potential to stimulate all arms of the immune system, were stable at the temperature of tropical countries, without any damage to their constituent proteins (112) . Recent nanotechnology advances have led to nanovaccines that can maintain their stability independent of temperature over long periods, and still produce a good immune response with a self-administrated single dose, and are expected to contribute to the fight against the ongoing COVID-19 pandemic, and could even prevent future pandemics. J o u r n a l P r e -p r o o f Based on the latest research and news some COVID-19 candidate vaccines (e.g. Pfizer-BioNTech and Moderna COVID-19 vaccines) have being administrated to people in many of countries. Some of them with additional information will bring in the following table 1. The lack of an effective treatment method and (until recently) a viable vaccine against COVID-19 has compelled scientists worldwide to seek other approaches to contain the pandemic. Generally, if the possibility of contact with an infectious virus is lower, the lower the chance of catching that disease. The complete protection of health workers, patients, and the rest of the population may be improved if currently employed PPE (e.g., gloves, face masks, face shields, and gowns) can serve as a physical barrier against disease agents and viral pathogens. The shortage in the worldwide supply of PPE has compelled many individuals to reuse their equipment, which is highly likely to be unsafe. Nanotechnology offers a way around this issue by modifying the surface of PPE not only to capture and inactivate viruses, but also to be reusable and washable without compromising the efficiency and safety (Figure 4 ). Some researchers at the University of Central Florida (UCF) developed washable and reusable nano-coatings composed of alternating layers of cationic and anionic nanoparticles, that could successfully trap and destroy viruses, and specifically SARS-CoV-2 (121) . In a recent study, zinc-oxide NPs were employed to create a face mask with good antimicrobial activity, and this new technology is expected to help the production of washable, reusable, and antimicrobial PPE by the end of 2020 (122) . Given the significant J o u r n a l P r e -p r o o f role of face-masks in controlling the COVID-19 pandemic, many nanotechnologists are scrambling to adapt their research to enhance the performance of this type of PPE. Rainy et al. fabricated a new type of highly-breathable mask based on cellulose nanofibers that was considered very comfortable and did not distress the wearer when used for long hours. The mask was also appropriate for persons with respiratory problems and for use in hot and humid conditions (123) . Other companies have also utilized nanotechnology to design additional options for face-masks. Table 2 lists nanotechnology-based face-masks that are currently available or will be soon launched onto the market. Unlike many other viruses, SARS-CoV-2 can remain active even on inanimate surfaces, such as plastic, fabrics, wood, glass, and metal surfaces for up to several hours or even days (130) scientists created a self-sterilizing nano-coating, called NanocleanSQ, which could kill 99.99% of viruses upon contact, and with a lifespan of several weeks or even years. The incorporation of a photocatalytic compound into this smart nanosystem improved its viruskilling activity even more when exposed to light (151) . The photocatalytic activity of TiO 2based nano-coatings has also been shown to help reduce the spread of SARS infections (152) . Additionally, the modification of often-touched surfaces such as bed rails, bed surfaces, supply carts, and doorknobs with highly-repellent nanomaterials could keep germs and viruses away (153, 154) . Table 3 summarizes some other nano-coatings with the potential to control the COVID-19 pandemic. Journal Pre-proof Viruses have been a serious threat to human health throughout the ages, but since the discovery of their biological structure it has been possible to make a more accurate diagnosis (165, 166) . Since the emergence of COVID-19, many scientists have been seeking reliable, sensitive, and selective diagnostic tests that can be used on a large scale. The standard method for the diagnosis of COVID-19 is the reverse transcription-polymerase chain reaction (RT-PCR). However, some false-negative and false-positive results have been reported for this test, suggesting its low sensitivity (167) . Nanobiosensors have shown some potential for the rapid-response and real-time detection of SARS-CoV-2 (168) . Thus far, many such tools have been developed using different read-out methods, including optical, electrochemical, J o u r n a l P r e -p r o o f electrochemiluminescence (ECL), quartz crystal microbalance (QCM), and surface plasmon resonance (SPR) techniques (168). An optical biosensor is an analytical system relying on a biorecognition sensing element integrated with an optical transducer system. The advantages of these devices include, small size, high specificity, high sensitivity, and cost-effectiveness (169) . Many optical sensors have been based on plasmonics, among which localized surface plasmon resonance (LSPR) has been widely used to detect specific viral strains in laboratory studies (170). Optical Recently Since conventional diagnostic techniques (e.g., quantitative real-time PCR) are time- with silver and fullerene NPs as a biosensor incorporated into a smartphone (180) . The combination of nanobiosensors with mobile devices may facilitate COVID-19 population screening, as well as the collection of data, and tracking infected cases. Field-effect-transistors (FETs), three-electrode potentiometric sensors, and amperometric systems are among the major types of electronic biosensors with advantages including, low cost, miniaturization, and possibility of mass production (181, 182) . In one recent study, Seo (97). In another study, a carbon-based three electrode biosensor was developed to detect SARS-CoV-2 in non-clinical samples (183) . Electrochemical techniques such as electrochemical impedance, cyclic voltammetry, and amperometry can provide label-free detection, and do not require any additional signaling molecules or a sandwich assay. In 2020, Tripathy and Singh showed that an electrochemical biosensing approach based on surface-modified gold NPs could be used for COVID-19 detection. They designed a sensing electrode that was highly stable even under harsh chemical conditions, together with a complementary thiolated nucleic acid probe that matched the target sequence. The sequence attached to the sensing electrode through goldthiol self-assembly. The viral RNA or the cDNA of SARS-CoV-2 could be detected after hybridization to the complementary thiolated probe using the electrochemical biosensor. The device was also equipped with a smartphone-based read-out for smart POC healthcare (184). One promising approach to control the pandemic is the manipulation of microscale fluids, or microfluidics (185) . Many microfluidic biosensors have been suggested to detect bacteria, foodborne pathogens, or viral infections (186) . These biosensors could be far superior to culture-based methods, and also to molecular techniques in terms of portability, precision, Due to the frequent mutations that occur in viruses called genetic plasticity, the sequence analysis of RNA viral genomes remains a challenge. Nanopore sequencing is a robust technology that enables the real-time reading of the base sequences in long DNA or RNA segments. In this technology, a change in the electrical current is monitored as the nucleic acids pass through a protein nanopore. Viral RNA can be detected in coronavirus-infected cells using nanopore-based direct RNA sequencing (DRS) approaches (190) . LamPORE has developed the first-ever nanopore sequencing machine for the detection of SARS-CoV-2 in samples, that may also contain influenza or other respiratory viruses. In this assay, nanopore sequencing was incorporated with the loop-mediated isothermal amplification procedure, creating a scalable, controllable, rapid, and highly-sensitive assay (191) . Researchers at the University of Maryland devised an accurate test for the detection of viruses in nasal swabs or saliva samples within 10 minutes. When the virus is present the RNA genetic sequence attaches to the plasmonic gold NPs and produces a color change of the suspension from purple to blue (192) . Upon acute infection, humans generate a specific IgM antibody against SARS-CoV-2, which can act as a reliable indicator. In one recent study, a colloidal gold-NP-based lateral-flow reported to be 100% and 93.3%, respectively. The advantages of this test included high specificity and stability, easy operation, low cost, and rapid response. It provided results within 15 min using only 10-20 μL of serum for each test (193) . Porous nanomaterials can be employed to recognize a wide range of pathogens. An interaction between the surface of metal-organic frameworks (MOFs), which have been functionalized with optical active molecules as quenchers or activators, and the pathogen could be detected (194) (195) (196) . For instance, a highly accurate nanosystem was developed based on MOF-5@Au-nanorods to detect SARS-CoV-2. The nanosystem allowed surfaceenhanced Raman scattering (SERS) as a powerful spectroscopic technique to measure a subattomolar concentration on MOF-5@Au-nanorods (197, 198) . The discovery of clustered, regularly interspaced short palindromic repeats (CRISPR) was a In addition to vaccine-based approaches, nanotechnology is also being investigated for new therapeutic approaches to fight the COVID-19 pandemic (205) (206) (207) (208) . Up to now, nanotechnology has been employed in several successful treatment methods for infections caused by the AIDS virus, respiratory viruses, and herpes simplex viruses (209) (210) (211) (212) . As for COVID-19, some nanotechnology-based therapeutic techniques are currently under J o u r n a l P r e -p r o o f investigation, including magnetic-based hyperthermia therapy, photothermal therapy, antiviral drug delivery, and gene editing of SARS-CoV-2 via CRISPR type systems. Magnetic NPs with good biocompatibility and low toxicity are often used in hyperthermia therapy (213, 214) . The underlying mechanism of magnetic hyperthermia is that doses of injected magnetic NPs can be accumulated in specific locations within the body by application of a static external magnetic field. Next the application of a powerful alternating external magnetic field produces heat within the NPs thus causing thermal damage to pathogenic organisms (215, 216) . This treatment technique has been employed in clinical practice to treat inoperable cancers such as glioblastoma multiforme or prostate tumors. Some (4) using a safe and non-invasive source to deliver the magnetic field. Photothermal therapy (PTT) is a minimally-invasive technique that leverages NPs to convert near-infrared (NIR) light into heat in order to destroy target cells (224) . Photodynamic therapy (PDT), on the other hand, takes advantage of photosensitizers, which produce reactive oxygen species (ROS) using photochemistry to kill viral infected cells. The application of PDT has some limitations due to the short lifespan of the ROS, while PTT allows for localized light-induced hyperthermia, which is not limited by the microenvironment because of using tissue-penetrating NIR light (225, 226) . NIR irradiation (650-900 nm) is generally preferred for clinical applications since it can penetrate tissues and is less harmful than shorter wavelengths of light (227) . Photothermal agents can rapidly generate intense heat under NIR laser irradiation, thereby inactivating viruses and killing pathogens by denaturing their enzymes, or damaging their cell membrane proteins, nucleic acids, or lipids (220, 228) . PTT is commonly used for cancer therapy and sometimes for killing bacteria, but the studies are still in very early stages for treatment of viral infections, The PTT method generally combines a pulsed laser with light-absorbing nanomaterials (229) . Although organic NPs are biocompatible and low-cost, metal NPs (e.g., gold NPs) have much higher absorption coefficients and are therefore required in much lower amounts (230, 231) . Another group of photothermal sensitizers are carbon-based nanomaterials, such as graphene oxide (GO) (232), or carbon nanotubes (CNTs) due to their good ability to convert NIR into heat (233) . PTT methods based on CNTs have demonstrated several advantages over magnetothermal therapy using magnetic NPs. Using magnetic fields to excite magnetic NPs to produce heat involves a slower heating rate with a higher depth of energy penetration than NIR, which increases the risk of off-target damage to healthy tissues (234) . In 2008, poly (241, 242) . In 2017, gold nanorods were employed for the photonic inactivation of murine leukemia virus (MLV) using an 805-nm NIR laser. It was found that NIR irradiation produced a plasmonic shock in the nanorods, which altered the virus membrane, thereby reducing its ability to bind to host cells (243) . Organic molecules and conjugated polymer NPs are considered a safe group of nanomaterials, which can absorb photons in the NIR range and generate heat using nonradiative energy transfer (244, 245) . Conjugated polymers are electrically conductive owing to multiple double bonds along the polymer backbone, leading to electron delocalization (246) . The use of nanotechnology for antiviral drug delivery has enabled the development of smart and targeted nanocarriers that minimize the side effects of antiviral drugs. Many of these drugs can also damage healthy non-infected cells, and cause other harmful side effects when used at high doses. This strategy also addresses an issue arising from the low water solubility of antiviral drugs posing difficulties for in vivo delivery (248, 249) . The unique properties of nanomaterials, including small size, biocompatibility, good solubility, easy surface functionalization, extended circulation time, and their ability to deliver required doses of a drug, make them outstanding candidates for drug delivery (250) . Given the success of nanotechnology-based drug delivery systems in the treatment of viral infections, summarized in Table 4 , it is anticipated that they will also be able to help treat COVID-19. Metal NPs can deliver therapeutic antiviral agents and drugs to target cells, as well as having intrinsic antiviral activity. Their size is generally smaller than organic NPs (1-100 nm), with a higher drug loading capacity (242, 251) . Some studies have focused on selenium NPs (SeNPs) for the delivery of therapeutic agents. It has been reported that these NPs could affect the function of the immune system cells, and reduce the generation of free radicals inside host cells by preventing mitochondrial depolarization (252, 253) . SeNPs have also shown the potential to inhibit the proliferation of hepatitis virus in human hepatoma cell lines (254) . Gold NPs can enter different types of cells and tissues, such as the central nervous system and can persist for some time These NPs have good biocompatibility coupled with the SPR effect and can be functionalized with various agents (e.g., polymers with antiviral properties) (211, 260) . In 2018, gold NPs were employed to deliver RBV to the African green monkey kidney cell line (Vero cells) to destroy the measles virus. It was found that the gold NPs-RBV at a dose of 99.5 µg/mL had a stronger antiviral effect compared to 500 µg/mL of free RBV (261) . Nevertheless, other metal NPs can suffer from poor biodegradability, low biological distribution, high accumulation within the body, and in some cases, high toxicity as a consequence of surface modification. Due to their high surface area to volume ratio, and ability to penetrate through cell membranes, CNTs can serve as suitable nanocarriers for the delivery of antiviral drugs (262) . Studies showed that the toxicity of oxidized CNTs and polymer-coated CNTs was within the accepted range for clinical application (263, 264) . For instance, isoprinosine is an antiviral Viruses such as HIV, HCV, HBV, as well as respiratory viruses can cause persistent disease by integrating their genome into the human genome of the host cells (295) . The CRISPR/Cas9 technology was originally developed based on a bacterial defense mechanism against invading viruses, and can now be used to treat persistent viral infections (296, 297) . The superiority of the CRISPR/Cas9 system over other treatment methods lies in its potential to target the viral RNA and DNA genomes directly, to eliminate the viruses and halt J o u r n a l P r e -p r o o f persistent infections (298) . Thus, this technology shows promise to control viral pandemics, e.g., SARS-CoV, SARS-CoV-2, or pandemic influenza in both the pre-integration and provirus stages (299, 300 In a recent study, a gene-editing system was developed based on Cas13e.1 (type VI) that could successfully cleave SARS-CoV-2 sequences as well as influenza A virus in cultured HEK293T and N2A cells. The Cas13e sequences were cloned into a pCX539 backbone via the Gibson Assembly method, and then transfected into cultured cells using lipofectamine 3000. The expressed Cas13e.1 could target more than 99% of the viral genome in a pool of 10 crRNAs with single nucleotide mismatches, which might also reduce the chance of the viruses escaping from antiviral destruction by mutation. (307) . J o u r n a l P r e -p r o o f CRISPR/Cas systems for COVID-19 gene editing can be delivered by either AAVs or by lipofectamine. Despite the high efficiency of AAV-based in vivo delivery systems, the possible long-term immunogenicity of viral carriers is a problem for the use of an antiviral gene-editing system (311) . On the other hand, the use of cationic lipofectamine for in vivo applications requires careful consideration because of its high toxicity and costs (312) . Although traditional delivery systems can transfer high concentrations of therapeutic agents, the instability of their cargo remains a major obstacle. The incorporation of CRISPR/Cas systems into NPs may lead to the introduction of safer and highly-efficient gene-editing platforms. Smart NPs, also known as stimuli-responsive NPs, have the ability to control the spatio-temporal release of therapeutic agents in response to environmental stimuli, thereby reducing the side effects of antiviral drugs and protecting healthy tissues (313, 314) . The triggering of these smart NPs by stimuli, can be categorized into two types: (1) internal stimuli, such as pH, redox potential, or enzyme activity; (2) external stimuli such as temperature gradient, light irradiation, magnetic field, or electrical field (315, 316) . Since COVID-19 mainly affects specific types of cells, tissues, and organs, controlled drug delivery via smart NPs could improve patient compliance (317-319). The differences in pH and glutathione (GSH) that exist between various cells and tissues of the body, allows scientists to design smart NPs that can precisely release drugs at predetermined sites. For example, the intracellular concentration of GSH in the blood and the extracellular matrix is 1-10 mM and 2-20 μM, respectively (320) . Additionally, there is a significant pH difference between different organs and tissues of the body; e.g., there is pH gradient within the gastrointestinal tract (from pH 2 -pH 7.4) which affects the absorption of drugs in different ways, and the pH of the cytosol (pH 7.4), lysosomes (pH 4.5-5), and endosomes (pH 5. [5] [6] are also different (321) . The targeted delivery of antiviral drugs such as abacavir (ABC) and lamivudine (3TC) in acidic environments (e.g., the vagina) was investigated by attaching pH-sensitive ester derivatives to gold glyco-nanoparticles as a new HIV treatment method (322) . The pHsensitive NPs prepared for oral drug delivery also tackled the issue of precipitation upon administration as well as incomplete absorption of drugs from the GI tract. These nanocarriers can dissolve hydrophobic drugs and remain stable at acidic pH, thus increasing their oral absorption and reducing the drug release in the stomach. As the pH increases, these NPs become ionized and then release their cargo. These pH-responsive polymeric J o u r n a l P r e -p r o o f nanospheres have been shown to improve the oral absorption of human HIV-1 protease inhibitors in animal models (323, 324) . There is a redox potential gradient between the intracellular and extracellular space, leading to redox-sensitive polymeric nanomaterials being investigated for controlled antiviral drug delivery (315, 325) . These nanocarriers undergo the cleavage of disulfide bonds upon exposure to a reducing agent such as GSH (325) . Miao Delivery systems based on external stimuli require external sources, such as light irradiation, temperature gradients, and magnetic fields, to release therapeutic agents. In recent years, smart drug-delivery systems have been attracting considerable attention, because of their noninvasive nature. Light-responsive and ultrasound-sensitive drug or gene delivery systems can release the agents exactly at the targeted site at the desired time upon exposure to an external source of energy (227, 314) . Some nanoplatforms rely on magnetic fields for the delivery of antiviral drugs into the brain due to the remarkable ability of magnetic NPs to cross the blood-brain barrier (BBB) (327, 328) . The stability and biocompatibility of magnetic NPs can be improved by coating with polymers or lipid-based nanomaterials (329, 330) . Last but not least, the incorporation of nanoparticles into magnetothermal therapy, photothermal therapy, drug delivery systems, and gene-editing platforms (e.g., CRISPR/Cas9) has shown early promise for the treatment of COVID-19 infections with minimal side effects. However, as a lesson learned from the emergence of SARS-CoV-2, ongoing research efforts should continue not only to halt the COVID-19 pandemic, but also to increase the state of preparedness for tackling new viruses that may emerge in the future. This may help to prevent the outbreak of future pandemics. Clover and GSK announce research collaboration to evaluate coronavirus (COVID-19) vaccine candidate with pandemic adjuvant system 24 February 2020 [Available from: https://www.gsk.com/en-gb/media/press-releases/clover-and-gsk-announce-researchcollaboration-to-evaluate-coronavirus-covid-19-vaccine-candidate-with-pandemic-adjuvant-system/. Silva JM, Videira M, Gaspar R, Préat V, Florindo HF. Immune system targeting by biodegradable nanoparticles for cancer vaccines. Journal of controlled release. 2013;168(2): 179-99. 46 . Peek LJ, Middaugh CR, Berkland C. Nanotechnology in vaccine delivery. Advanced drug delivery reviews. 2008;60 (8) COVID-19 vaccine development and a potential nanomaterial path forward Coronavirus disease 2019 (COVID-19): current status and future perspectives A novel coronavirus outbreak of global health concern. The Lancet An interactive web-based dashboard to track COVID-19 in real time. The Lancet infectious diseases Presumed asymptomatic carrier transmission of COVID-19 Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia Covid-19: four fifths of cases are asymptomatic, China figures indicate Universal screening for SARS-CoV-2 in women admitted for delivery Identification of Coronavirus Isolated from a Patient in Korea with COVID-19. Osong public health and research perspectives A comparison of COVID-19, SARS and MERS Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine The COVID-19 pandemic, psychological stress during pregnancy, and risk of neurodevelopmental disorders in offspring: a neglected consequence Origin and evolution of pathogenic coronaviruses COVID-19 and the cardiovascular system Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms Kidney impairment is associated with in-hospital death of COVID-19 patients Liver injury in COVID-19: management and challenges COVID-19 and the liver: little cause for concern Covid-19 and the digestive system Nanomedicine and advanced technologies for burns: Preventing infection and facilitating wound healing Advanced Nanobiomaterials: Vaccines, Diagnosis and Treatment of Infectious Diseases Nanotechnology-based antiviral therapeutics. Drug delivery and translational research Photoluminescent carbon quantum dot/poly-l-Lysine core-shell nanoparticles: A novel candidate for gene delivery COVID-19 vaccine development and a potential nanomaterial path forward Nanovaccines: recent developments in vaccination Risk of COVID-19 among front-line health-care workers and the general community: a prospective cohort study. The Lancet Public Health Vaccine adjuvants: key tools for innovative vaccine design. Current topics in medicinal chemistry Immunemediated approaches against COVID-19 Prophylactic Vaccines, Successes, Errors, and Complications Serum Institute of India Initiates Manufacturing of Codagenix's Intranasal Live-Attenuated COVID-19 Vaccine Candidate Novavax COVID-19 Vaccine Demonstrates 89.3% Efficacy in UK Phase 3 Trial Gold nanoparticles as a vaccine platform: influence of size and shape on immunological responses in vitro and in vivo Improvement of different vaccine delivery systems for cancer therapy Virus-like particles in vaccine development. Expert review of vaccines Currently approved prophylactic HPV vaccines. Expert review of vaccines Influenza virus-like particle can accommodate multiple subtypes of hemagglutinin and protect from multiple influenza types and subtypes Novel chimeric virus-like particles vaccine displaying MERS-CoV receptor-binding domain induce specific humoral and cellular immune response in mice Recent advances in the vaccine development against Middle East respiratory syndrome-coronavirus MERS-CoV virus-like particles produced in insect cells induce specific humoural and cellular imminity in rhesus macaques Immune responses against severe acute respiratory syndrome coronavirus induced by virus-like particles in mice SpyBiotech and Serum Institute of India announce that the first subjects have been dosed in a Phase I/II trial of a novel virus-like particle vaccine targeting COVID-19 DNA vaccines: a review Immunobiology: the immune system in health and disease1999 mRNA vaccines-a new era in vaccinology Immunogenicity of a DNA vaccine candidate for COVID-19 Knocking down barriers: advances in siRNA delivery Interfering cancer with polymeric siRNA nanomedicines Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial. The Lancet INO-4800 COVID-19 Vaccine Study of COVID-19 DNA Vaccine (AG0301-COVID19 ZyCoV-D, the made-in-India Covid vaccine by Zydus Cadila, likely to hit markets in Safety and Immunogenicity Study of GX-19, a COVID-19 Preventive DNA Vaccine in Healthy Adults A Clinical Trial of a Prophylactic Plasmid DNA Vaccine for COVID-19 The Safety and Immunogenicity of a DNA-based Vaccine (COVIGEN) in Healthy Volunteers (COVALIA) Surface-engineered gold nanorods: promising DNA vaccine adjuvant for HIV-1 treatment Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses COVID-19 vaccine development and a potential nanomaterial path forward Induction of HIV-1 gag specific immune responses by cationic micelles mediated delivery of gag mRNA A thermostable mRNA vaccine against COVID-19 Leveraging mRNAs sequences to express SARS-CoV-2 antigens in vivo Preclinical evaluation of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B. bioRxiv Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine induces equivalent preclinical antibody titers and viral neutralization to recovered COVID-19 patients Arcturus Therapeutics Announces Positive Interim ARCT-021 (LUNAR-COV19) Phase Study Results for Both Single Shot and Prime-boost Regimens, and Up to $220 Million in Additional Financial Commitments from Singapore November 9 CoV-2 vaccine candidate CVnCoV induces high levels of virus-neutralising antibodies and mediates protection in rodents. npj Vaccines COVID-19 vaccine BNT162b1 elicits human antibody and TH 1 T cell responses Durability of responses after SARS-CoV-2 mRNA-1273 vaccination Rapid detection of COVID-19 causative virus (SARS-CoV-2) in human nasopharyngeal swab specimens using field-effect transistor-based biosensor Review of microneedle based transdermal drug delivery systems A review on microfabrication of thermoplastic polymer-based microneedle arrays Dissolvable microneedle arrays for intradermal delivery of biologics: fabrication and application Nanotechnology solutions for mucosal immunization M2e-immobilized gold nanoparticles as influenza A vaccine: Role of soluble M2e and longevity of protection Immune response by nasal delivery of hepatitis B surface antigen and codelivery of a CpG ODN in alginate coated chitosan nanoparticles Stability of plant virus-based nanocarriers in gastrointestinal fluids Systemic trafficking of plant virus nanoparticles in mice via the oral route Nanopatches: engineering devices for targeted delivery to skin, improving vaccines A dissolvable needle-free nanotechnology patch for vaccine delivery Biodegradable viral nanoparticle/polymer implants prepared via melt-processing Novel technology for storage and distribution of live vaccines and other biological medicines at ambient temperature Nanovaccines-an overview Icosahedral virus particles as addressable nanoscale building blocks Nanomedicine: Promise of the future in disease management Fact check: Clarifying claims around Pfizer vaccine deaths and side effects DECEMBER 10 Arab nations first to approve Chinese COVID vaccine-despite lack of public data Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. The Lancet Review of COVID-19 Vaccines Approved in the United States of America for Emergency Use Nano-Coating Captures and Kills Viruses on Personal Protective Equipment (PPE) Israeli antimicrobial washable facemasks enter US market New mask material can remove virus-size nanoparticles VIRUS KILLER membrane 2020 Announcing the Launch of the "Zexeed™ YAMASHIN Filter Promethean Particles puts its nano-copper to the test in the fight against viruses 2020 Smart Mask for COVID-19 Virucidal effect against Coronavirus SARS-CoV-2 of a silver nanocluster/silica composite sputtered coating. Open Ceramics Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1 Silver nanoparticles as novel antibacterial and antiviral agents. HANDBOOK OF NANOBIOMEDICAL RESEARCH: Fundamentals, Applications and Recent Developments: Volume 1 Materials for Nanomedicine Mode of antiviral action of silver nanoparticles against HIV-1 Antiviral activity of mycosynthesized silver nanoparticles against herpes simplex virus and human parainfluenza virus type 3 Antiviral activity of silver nanoparticle/chitosan composites against H1N1 influenza A virus Antiviral activity of graphene-silver nanocomposites against non-enveloped and enveloped viruses Antiviral activity of cuprous oxide nanoparticles against hepatitis C virus in vitro Nanoparticles as antiviral agents against adenoviruses Nanoparticles and surfaces presenting antifungal, antibacterial and antiviral properties Polyethylene glycol-coated zinc oxide nanoparticle: an efficient nanoweapon to fight against herpes simplex virus type 1 Inhibition of H1N1 influenza virus infection by zinc oxide nanoparticles: another emerging application of nanomedicine Prophylactic, therapeutic and neutralizing effects of zinc oxide tetrapod structures against herpes simplex virus type-2 infection Zinc and respiratory tract infections: Perspectives for COVID-19 Investigation of quaternary ammonium silane-coated sand filter for the removal of bacteria and viruses from drinking water A Surface Coating that Rapidly Inactivates SARS-CoV-2 HKUST Develops New Smart Anti-Microbial Coating in the Fight Against COVID New anti-COVID-19 nanocoating surface developed at Ben-Gurion University of the Negev 12-MAY-2020 Nanomaterials for targeted detection and photothermal killing of bacteria Towards effective photothermal/photodynamic treatment using plasmonic gold nanoparticles Photoactive antimicrobial nanomaterials Construction of nanomaterials with targeting phototherapy properties to inhibit resistant bacteria and biofilm infections Guelph Researchers: Self-sterilizing Nano-coating and No More Coronavirus-infected Surfaces Smart Polymeric Coatings to Enhance the Antibacterial, Anti-fogging and Self-Healing Nature of a Coated Surface Researchers Create Ultimate Non-Stick Coating That Repels Everything -Even Viruses and Bacteria DECEMBER 16 Flexible Hierarchical Wraps Repel Drug-Resistant Gram-Negative and Positive Bacteria COVID 19) Protection For use during public health emergency to help destroy airborne SARS-CoV-2, the virus causing COVID-19 2020 LI mall uses 'self-cleaning' technology in some of its highest-touch areas 2020 FN1® Coating 2020 Coronavirus: Nanotech Surface Sanitizes Milan with Nanomaterials Remaining Self-sterilized for Years 2020 MVX Protex Antimicrobial Coat Spray 2020 COVID-19, immune system response, hyperinflammation and repurposing antirheumatic drugs Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein Real-time RT-PCR in COVID-19 detection: issues affecting the results Nanoscale virus biosensors: state of the art Sensitive optical biosensors for unlabeled targets: A review. analytica chimica acta Optical biosensors Fluorescent imaging of single nanoparticles and viruses on a smart phone Fluorescent imaging of single nanoparticles and viruses on a smart phone A new biosensor for the COVID-19 virus: Detection in the environment: ScienceDaily Detection of the nucleocapsid protein of severe acute respiratory syndrome coronavirus in serum: comparison with results of other viral markers Dual-Functional Plasmonic Photothermal Biosensors for Highly Accurate Severe Acute Respiratory Syndrome Coronavirus 2 Detection Development of Point-of-Care Biosensors for COVID-19 Development and evolution of a novel loop mediated isothermal amplification method for rapid detection of severe acute respiratory syndrome corona virus Evaluation of real-time reverse transcriptase PCR and real-time loop-mediated amplification assays for severe acute respiratory syndrome coronavirus detection A smartphone-based rapid telemonitoring system for Ebola and Marburg disease surveillance Flexible Ag-C 60 nano-biosensors based on surface plasmon coupled emission for clinical and forensic applications Ion-sensitive field-effect transistors fabricated in a commercial CMOS technology field-effect transistor biosensing: Devices and clinical applications eCovSens-Ultrasensitive Novel In-House Built Printed Circuit Board Based Electrochemical Device for Rapid Detection of nCovid-19 antigen, a spike protein domain 1 of SARS-CoV-2. bioRxiv Label-Free Electrochemical Detection of DNA Hybridization: A Method for COVID-19 Diagnosis Revisiting lab-on-a-chip technology for drug discovery Microfluidic Based Biosensors as Point of Care Devices for Infectious Diseases Management Evaluation of the NanoChip 400 system for detection of influenza A and B, respiratory syncytial, and parainfluenza viruses Evaluation of a novel micro/nanofluidic chip platform for the detection of influenza A and B virus in patients with influenza-like illness COVID-19: New lab-on-chip improves detection sensitivity, detects virus rapidly April Direct RNA nanopore sequencing of full-length coronavirus genomes provides novel insights into structural variants and enables modification analysis Oxford Oxford (COVID-19): Oxford Nanopore Technologie Current laboratory diagnostics of coronavirus disease Rapid Detection of IgM Antibodies against the SARS-CoV-2 Virus via Colloidal Gold Nanoparticle-Based Lateral-Flow Assay Metal-organic frameworks: opportunities and challenges for surface-enhanced Raman scattering-a review The Chemistry of Reticular Framework Nanoparticles: MOF, ZIF, and COF Materials Luminescent switch sensors for the detection of biomolecules based on metal-organic frameworks Materials, applications, and the future Point-of-Use Rapid Detection of SARS-CoV-2: Nanotechnology-Enabled Solutions for the COVID-19 Pandemic Programmable inhibition and detection of RNA viruses using Cas13 All-in-One dual CRISPR-cas12a (AIOD-CRISPR) assay: a case for rapid, ultrasensitive and visual detection of novel coronavirus SARS-CoV-2 and HIV virus Rapid detection of 2019 novel coronavirus SARS-CoV-2 using a CRISPR-based DETECTR lateral flow assay Development of CRISPR as a prophylactic strategy to combat novel coronavirus and influenza An ultrasensitive, rapid, and portable coronavirus SARS-CoV-2 sequence detection method based on CRISPR-Cas12. bioRxiv Development and evaluation of a CRISPRbased diagnostic for 2019-novel coronavirus. medRxiv Treatment with convalescent plasma for COVID-19 patients in Wuhan Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. The Lancet A strategic approach to COVID-19 vaccine R& COVID-19 vaccine design: the Janus face of immune enhancement Role of metal and metal oxide nanoparticles as diagnostic and therapeutic tools for highly prevalent viral infections Nanotechnology Approaches for the Delivery of Exogenous siRNA for HIV Therapy Nano-based approach to combat emerging viral (NIPAH virus) infection Nanotechnology for COVID-19: Therapeutics and Vaccine Research Magnetic nanoparticle-based hyperthermia for cancer treatment Magnetic nanoparticle-based therapeutic agents for thermochemotherapy treatment of cancer MAGNETIC NANOPARTICLE HYPERTHERMIA IN CANCER TREATMENT Thermal therapy with magnetic nanoparticles for cell destruction Magnetic nanoparticles in cancer therapy: how can thermal approaches help? Targeting and Enrichment of Viral Pathogen by Cell Membrane Cloaked Magnetic Nanoparticles for Enhanced Detection Application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity Stability of SARS-CoV-2 in different A simple magnetic nanoparticles-based viral RNA extraction method for efficient detection of SARS-CoV-2. bioRxiv Clinical hyperthermia of prostate cancer using magnetic nanoparticles: presentation of a new interstitial technique Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme Nanomaterials formulations for photothermal and photodynamic therapy of cancer Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death Mitochondrial Reactive Oxygen Species and Photodynamic Therapy Stimulus-responsive sequential release systems for drug and gene delivery Aggregation and Cellular Toxicity of Pathogenic or Non-pathogenic Monitoring and Evaluation of Biomaterials and their Performance In Vivo Photothermal therapy with gold nanoparticles as an anticancer medication Current Use of Carbon-Based Materials for Biomedical Applications-A Prospective and Review Photothermal therapy of melanoma tumor using multiwalled carbon nanotubes Magnetic fluid hyperthermia therapy for malignant brain tumors-an ethical discussion Photoinduced antiviral carbon nanohorns Graphene-Based Photothermal Agent for Rapid and Effective Killing of Bacteria Graphene-based "Hotplate" for the Capturing and Destruction of the Herpes Simplex Virus Type 1 Protein Degradation and RNA Efflux of Viruses Photocatalyzed by Graphene-Tungsten Oxide Composite Under Visible Light Irradiation Near-infrared light-responsive inorganic nanomaterials for photothermal therapy Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles Streptavidin-conjugated gold nanoclusters as ultrasensitive fluorescent sensors for early diagnosis of HIV infection Plasmonic Enhancement of Selective Photonic Virus Inactivation Organic molecule-based photothermal agents: an expanding photothermal therapy universe Molecular Interactions in Organic Nanoparticles for Phototheranostic Applications Well-Defined Gold Nanorod/Polymer Hybrid Coating with Inherent Antifouling and Photothermal Bactericidal Properties for Treating an Infected Hernia Nanomaterials Designed for Antiviral Drug Delivery Transport across Biological Barriers Acta medica Croatica : casopis Hravatske akademije medicinskih znanosti The importance of nanoparticle shape in cancer drug delivery Anti-HIV-1 nanotherapeutics: promises and challenges for the future Th1 Immune Response Induction by Biogenic Selenium Nanoparticles in Mice with Breast Cancer: Preliminary Vaccine Model Sodium selenite suppresses hepatitis B virus transcription and replication in human hepatoma cell lines Inhibitory activity of selenium nanoparticles functionalized with oseltamivir on H1N1 influenza virus Functionalized selenium nanoparticles enhance the anti-EV71 activity of oseltamivir in human astrocytoma cell model. Artificial cells, nanomedicine, and biotechnology Ribavirin: a drug active against many viruses with multiple effects on virus replication and propagation. Molecular basis of ribavirin resistance. Current opinion in virology Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Restriction of H1N1 influenza virus infection by selenium nanoparticles loaded with ribavirin via resisting caspase-3 apoptotic pathway Applications of Noble Metal-Based Nanoparticles in Antiviral activity of Ribavirin nano-particles against measles virus Advancement in carbon nanotubes: basics, biomedical applications and toxicity Synthesis and anti-HIV activity of carboxylated and drug-conjugated multi-walled carbon nanotubes Regulation of angiogenesis through the efficient delivery of microRNAs into endothelial cells using polyaminecoated carbon nanotubes. Nanomedicine : nanotechnology, biology, and medicine Anti-betanodavirus activity of isoprinosine and improved efficacy using carbon nanotubes based drug delivery system β-Cyclodextringrafted on multiwalled carbon nanotubes as versatile nanoplatform for entrapment of guaninebased drugs Emerging investigator series: polymeric nanocarriers for agricultural applications: synthesis, characterization, and environmental and biological interactions Nanoparticles in medicine: therapeutic applications and developments Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier Characterization of branched poly(lactide-co-glycolide) polymers used in injectable, long-acting formulations Nanoparticle vaccines Factors Affecting the Clearance and Biodistribution of Polymeric Nanoparticles Antiviral efficacy of nanoparticulate vacuolar ATPase inhibitors against influenza virus infection Development of Biodegradable Nanoparticles for Liver-Specific Ribavirin Delivery Liposomes for Enhanced Bioavailability of Water-Insoluble Drugs: In Vivo Evidence and Recent Approaches Liposomal Formulations for Nose-to-Brain Delivery: Recent Advances and Future Perspectives Intranasal Antiviral Drug Delivery and Coronavirus Disease 2019 (COVID-19): A State of the Art Review Acyclovir Liposomes for Intranasal Systemic Delivery: Development and Pharmacokinetics Evaluation. Drug delivery Lipid-Coated Mesoporous Silica Nanoparticles for the Delivery of the ML336 Antiviral to Inhibit Encephalitic Alphavirus Infection Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: applications, advantages and disadvantages Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats: A rapid in vivo screening method for nanotoxicity Potential neurotoxicity of nanoparticles Vitro and In Vivo Short-Term Pulmonary Toxicity of Differently Sized Colloidal Amorphous SiO₂. Nanomaterials Lipid nanoparticles biocompatibility and cellular uptake in a 3D human lung model Nanostructured lipid carriers-based drug delivery for treating various lung diseases: A State-of-the-Art Review Hydroxychloroquine cardiotoxicity presenting as a rapidly evolving biventricular cardiomyopathy: key diagnostic features and literature review First Principle Simulation of Coated Hydroxychloroquine on Ag, Au and Pt Nanoparticle as a Potential Candidate for Treatment of Squalene-based multidrug nanoparticles for improved mitigation of uncontrolled inflammation in rodents Reversal of H1N1 influenza virus-induced apoptosis by silver nanoparticles functionalized with amantadine Hyaluronic Acid-Gold Nanoparticle/Interferon α Complex for Targeted Treatment of Hepatitis C Virus Infection Nanoformulation of antiretroviral drugs enhances their penetration across the blood brain barrier in mice Fabrication and in vivo evaluation of Nelfinavir loaded PLGA nanoparticles for enhancing oral bioavailability and therapeutic effect Nanoparticle-based topical ophthalmic formulation for sustained release of stereoisomeric dipeptide prodrugs of ganciclovir Formation and In-vitro Evaluation of Zidovudine-Lamivudine Nanoparticles. Indian journal of pharmaceutical education Viral Integration and Consequences on Host Gene Expression. Viruses: Essential Agents of Life CRISPR/Cas9-The ultimate weapon to battle infectious diseases? CRISPR/Cas9-Based Antiviral Strategy: Current Status and the Potential Challenge The Impact of CRISPR-Cas System on Development of CRISPR as a prophylactic strategy to combat novel coronavirus and influenza Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection Mechanisms of viral mutation. Cellular and molecular life sciences : CMLS Efficient gene editing via non-viral delivery of CRISPR-Cas9 system using polymeric and hybrid microcarriers CRISPR-Cas9 gene editing: Delivery aspects and therapeutic potential A Single Administration of CRISPR/Cas9 Lipid Nanoparticles Achieves Robust and Persistent In Vivo Genome Editing A non-viral CRISPR/Cas9 delivery system for therapeutically targeting HBV DNA and pcsk9 in vivo Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility Novel miniature CRISPR-Cas13 systems from uncultivated microbes effective in degrading SARS-CoV-2 sequences and influenza viruses2020 RNA-Targeting CRISPR-Cas Systems and Their Applications RNA targeting with CRISPR-Cas13 Virus against virus: a potential treatment for 2019-nCov (SARS-CoV-2) and other RNA viruses In vivo genome editing using Staphylococcus aureus Cas9 Preliminary study of a novel transfection modality for in vivo siRNA delivery to vocal fold fibroblasts. The Laryngoscope Stimuli-Responsive Drug Release from Smart Polymers Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems Smart Internal Stimulus-Responsive Nanocarriers for Drug and Gene Smart External Stimulus-Responsive Nanocarriers for Drug and Gene COVID-19 and Multiorgan Response COVID-19 and Liver Dysfunction: Current Insights and Emergent Therapeutic Strategies COVID-19: Abnormal liver function tests Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery Smart drug delivery systems: from fundamentals to the clinic Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs pH-sensitive vesicles, polymeric micelles, and nanospheres prepared with polycarboxylates pH-sensitive nanoparticles: an effective means to improve the oral delivery of HIV-1 protease inhibitors in dogs Design of Controlled Drug Delivery System Based on Disulfide Cleavage Trigger Redox-responsive chitosan oligosaccharide-SS-Octadecylamine polymeric carrier for efficient anti-Hepatitis B Virus gene therapy Magnetic Nanoparticles in the Central Nervous System: Targeting Principles, Applications and Safety Issues Evaluation of Targeted Delivery to the Brain Using Magnetic Immunoliposomes and Magnetic Force. Materials (Basel) Biocompatibility and Toxicity of Magnetic Nanoparticles in Regenerative Medicine Magnetic Nanoparticles: Synthesis, Surface Modifications and Application in Drug Delivery Magnetic nanoformulation of azidothymidine 5'-triphosphate for targeted delivery across the blood-brain barrier