key: cord-0762322-vmoaadk1
authors: Saravanan, Muthupandian; Mostafavi, Ebrahim; Vincent, Savariar; Negash, Hadush; Andavar, Rajapriya; Perumal, Venkatesan; Chandra, Namas; Narayanasamy, Selvaraju; Kalimuthu, Kalishwaralal; Barabadi, Hamed
title: Nanotechnology-based approaches for emerging and re-emerging viruses: Special emphasis on COVID-19
date: 2021-04-28
journal: Microb Pathog
DOI: 10.1016/j.micpath.2021.104908
sha: 62d54f039e3475f26dccaaf5871d8eb4e7443b90
doc_id: 762322
cord_uid: vmoaadk1

In recent decades, the major concern of emerging and re-emerging viral diseases has become an increasingly important area of public health concern, and it is of significance to anticipate future pandemic that would inevitably threaten human lives. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged virus that causes mild to severe pneumonia. Coronavirus disease (COVID-19) became a very much concerned issue worldwide after its super-spread across the globe and emerging viral diseases have not got specific and reliable diagnostic and treatments. As the COVID-19 pandemic brings about a massive life-loss across the globe, there is an unmet need to discover a promising and typically effective diagnosis and treatment to prevent super-spreading and mortality from being decreased or even eliminated. This study was carried out to overview nanotechnology-based diagnostic and treatment approaches for emerging and re-emerging viruses with the current treatment of the disease and shed light on nanotechnology's remarkable potential to provide more effective treatment and prevention to a special focus on recently emerged coronavirus.

Nanotechnology is defined as the application of particles with nanometer range dimension [1] , while nanomedicine is the application of nanostructured materials to diagnose, treat, and prevent diseases [2] . Nanoparticles are small size particles (which can facilitate drug delivery into anatomically privileged sites) [1, 3] with large surface area to volume ratios (which ensures that large drug payloads can be accommodated) [4] and are tunable surface charge (to facilitate cellular entry across the negatively charged cellular membrane) [5] . Hence, nanoparticles are preferable for viral treatment than macromolecules. Nanotechnology offers some advantages to combat emerging and re-emerging viruses including a) design of innovative drugs with increased activity and decreased toxicity [6, 7] ; b) design of smart nano-based sensors for early detection of viral infections [8, 9] ; and c) design of efficient personal protective equipments to avoid viral contamination such as nanoenabled masks [10, 11] . Nanomedicines have shown a significant accomplishment in management of viral infections [12] . Nanomedicines can overcome the site-specific delivery of the antiviral drugs.

For the case of COVID-19 disease, if the scientists introduce an efficient drug against SARS-CoV-2 virus, then the optimized targeted drug delivery systems based on nanomedicines can be helpful to overcome the site-specific delivery challenge. Nanomedicines are also beneficial for the controlled release and maintenance of the antiviral drugs in the targeted sites which have a significant role in the management of viral infections. Because, a high dose of off-targeted antiviral drugs may result in severe side effects, which can be worse than a viral infection [10] .

J o u r n a l P r e -p r o o f epidemic is going on, contact with confirmed cases, or contaminated objectives followed by precise laboratory setting [16] .

Real-time PCR assay was subsequently developed by using samples from respiratory (particularly lower respiratory tract) and distributed in Wuhan. Also, serological diagnostics are rapidly being developed but are not yet widely used; but much more researches are undergoing in different areas for treatment, vaccine and diagnostic techniques production for COVID-19 [17] . The commonly applied laboratory diagnostic techniques for COVID -19 include Molecular (RT-PCR/Real-time PCR), Serologic tests and viral cell culture, and chest X-ray or Thoracic CT scan. From all the laboratory tests, molecular diagnosis is the most recommendable and reliable way for COVID-19, whereas antibody testing shows low sensitivity, and Viral cell culturing is time-consuming [16] . In short, clinical diagnosis (high body temperature, dry cough, and difficulty of breathing) and history related to a particular geographical location (COVID-19 infected) are the primary forerunners of early diagnosing of the COVID-19, particularly where there is a lack of advanced laboratory setting.

In general, suddenly emerging viral diseases have not found specific and reliable treatments.

Besides, most, if not all, viral-caused diseases don't have reliable and very much effective treatment options [18] . Although there are no specific antiviral or immune-modulating agents proven yet for COVID-19, all patients are monitored by regular pulse oximetry. In China, patients were being treated based on National Clinical guidelines recommended by China National Health Commission (NHC); the guidelines include supportive care by clinical category (mild, moderate, severe and critical), as well as the role of investigational treatments such as chloroquine, phosphate, lopinavir/ritonavir, alpha interferon, ribavirin, arbidol [17] .

As the COVID-19 brings about a huge life-loss across the worldwide, it is very much necessary to discover a promising and typically effective treatment for decreasing the super-J o u r n a l P r e -p r o o f spreading and mortality or even its elimination. Altogether, there is a lot of researches on COVID-19 treatment being undertaken, where some of them reached clinical trials. Recent research revealed inhibitory action of remdesivir and chloroquine on the growth of SARS-CoV-2 in vitro, and an early clinical trial conducted in COVID- 19 Chinese patients showed that chloroquine had a significant effect, both in terms of clinical outcome and viral clearance [19, 20] . Hydroxychloroquine also presented effective antiviral activity against SARS-CoV-2 with better clinical safety, and it allows a high daily dose [21] . Another study conducted in France recently revealed that Hydroxychloroquine and azithromycin in combination showed very effective antiviral activity against SARS CoV-2 after 100% of patients treated with Hydroxychloroquine and azithromycin combination were Virologically cured comparing with 57 .1% in patients treated with Hydroxychloroquine only [22] .

Since the outbreak of Coronavirus, researchers have tried to develop nano-based treatments.

Nanoparticles like carbon quantum dots are suggested to be of excellent solubility in water.

Hence, they can be perfect candidates for winning the battle against Coronavirus because they can easily enter the cell through endocytosis and interact with the virus's protein, thereby preventing viral genome replication and inhibiting protein S receptor interaction [23] .

Nanoparticle-based treatment and vaccine development have been expected to improve efficacy, immunization strategies, and targeted delivery to promote immune responses for coronaviruses [24, 25] . Gold nanoparticles (AuNPs) have become the choice for alternative treatments because of their physicochemical properties, which prevent antibody production against viral infections [24] . Nanoparticles exert their antiviral activity by triggering the Production of pro-inflammatory cytokines and TH1 cytokines [26] .

J o u r n a l P r e -p r o o f HIV treatment is based on the action of drugs that target the life cycle and the multiplication process of the viral antigen. Currently, the antiretroviral therapy (ART) includes nucleotide reverse transcriptase inhibitors [27] , non-nucleoside inhibitors [28] , protease inhibitors [29] , entry/fusion inhibitors [30] , CCR5 antagonists [31] , and integrase inhibitors [32, 33] . To increase the efficacy of treatment and subsequently improve the quality of life, a combination of three or more drugs, called highly active ART (HAART) among HIV infected individuals will be employed [34] . Despite its effectiveness, the treatment is not devoid of unwanted occurrences due to suboptimal adherence, heavy pill burdens, toxicity, treatment side effects, and drug resistance development. Hence, it needs to have novel methods to enhance the inhibition of HIV infection, one of which is nanotechnology.

Modern drug design, which can incorporate ART drug delivery with nano-systems, can decrease the dosage requirements and toxic side effects associated with current heavy pill burdens to improve the treatment's safety and efficacy [35] .

Previous studies supported the evidence of effective treatment by nanotechnology. Chiodo et al. conducted a study on the NRTI drugs abacavir (ABC) and lamivudine (3TC) attaching to glucose nanoparticles (GNPs) in vitro. There was efficient function through the drug's primary hydroxyl groups via an ester bond that can be cleaved off in acidic conditions. After the experiment, the researcher illustrated a new level of multi-functionalization of GNPs as multivalent drug delivery systems for the treatment of HIV [36] . It was previously known that the regulatory T (Treg) cells were a specialized subpopulation of T-cells [37] . These T cells are components of the immune system and susceptible to HIV infection [38] . HIV infection leads to immune hyperactivation, which can subsequently result in erosion, depletion, or exhaustion of T-cells by preventing HIV disease progression [39] .

Other researchers demonstrated that carbosilane dendrimers could be used to prevent Treg cell infection with HIV in vitro. The negative phenotypic effects and decreased functionality of these cells due to HIV infection were also decreased with the application of these dendrimers. In addition, high bio-compatibility and a significant reduction in p24 antigen production was observed in cell culture and intracellularly [40] . [41] . Jayant et al. [42] demonstrated that an ARV (tenofovir) and an investigational latency-reversing drug (vorinostat) could be co-encapsulated on iron oxide nanoparticles [43] .

Similarly, there have been other studies that investigated nanoparticles as novel agents in ARV drug delivery [44, 45] , and small molecule HIV inhibitors [46, 47] for effective treatment of HIV.

The following nanoparticles are the most frequently used treatment options for treating viral infections.

AgNPs are the most effective nano-based inorganic metals against viral infections. These Coxsackievirus, and Saccharomyces cerevisiae dsRNA viruses to date [48] . It was shown that the silver cations released from AgNPs interact directly with phosphorus and sulfur groups of biomolecules such as DNA and RNA. The antiviral mechanism of AgNPs may be due to the interference of AgNPs with viral replication cycle in different stages such as virus binding to the cell membrane and its entry inside the cell, protein synthesis as well as DNA and RNA replication [49] . Figure 1A represented a schematic mechanism of antiviral activity of AgNPs on different stages of virus replication [50] . Moreover, it was stated that AgNPs prevented the entry of HIV to susceptible cells by interacting with glycoproteins in HIV envelopes, which avoid their binding and fusion with cell membrane [49] . Rónavári et al. investigated the antiviral activity of two green synthesized AgNPs using coffee (C-AgNPs) and green tea (GT-AgNPs) extracts against five S. cerevisiae dsRNA viruses that are in charge of the killer phenotype of the host strain. The obtained AgNPs were spherical with an average size of 3.2±1.2 and 12.7±5.8 nm for C-AgNPs and GT-AgNPs, respectively. In this study, the effect of AgNPs was observed on viral replication by loss of killer phenotype of the host strain ( Figure 1B ). C-AgNPs and GT-AgNPs caused five and three strains with altered phenotypes in the tested strains, respectively. Consequently, the strains treated with C-AgNPs were examined for the stability of the altered phenotype. After around 112 generations, only one strain maintained the nonkiller phenotype ( Figure 1B (d), #2). As shown in Figure 1B [K]). Moreover, in all of the five tested strains, the viral genomes were detected representing that the loss of killer phenotype was not due to viral eradication ( Figure 1B Figure 1D showed a schematic representation of interaction between tannic acid modified AgNPs or tannic acid and HSV-2 virion [56] . Ochoa-Meza1 et al. reported that AgNPs at the concentration of 12 ng/mL increased 20% survival of white spot syndrome virus infected Penaeus vannamei shrimps by activation of its immunological system, while the same concentration treated healthy shrimps did not show any histological evidence of damage [57] .

Unlike AgNPs, these nanoparticles have rarely been used for direct antiviral activity.

However, they are effective against HIV, H1N1, H3N2, H5N1, dengue virus, bovine viral diarrhea virus, and foot-and-mouth disease virus [58, 59] . Their mechanism of action is suggested to be by blocking gp120 attachment with CD4, which results in inhibited viral entry [58] , arresting replication at post-entry stage, mostly linked with transcription within the host cell [59, 60] , in bio-sensing, bio-imaging and catalytic activities [60] . Halder et al. Figure   2A ) [63] . Hemagglutinin is a highly conserved surface protein in many influenza viruses that can be considered as an effective target for designing novel antiviral drugs. Notably, hemagglutinin comprises six disulfide bonds. On the other hand, AuNPs have exhibited a high affinity to bind to the disulfide bonds due to gold-thiol interactions. Kim 

Iron-based nanoparticles have an effective antiviral effect. These particles have direct activity against bacteriophages, zika virus, HCV, and H5N2. They also have applications in hybridized form [66, 67] . Kumar 

Titanium dioxide (TiO 2 ) a white pigmented molecule which was effectively used as nanoparticle-based against influenza virus and bacteriophages [71, 72] . Moreover, researchers cannot rule out their toxicity. Hence, their biomedical application as an antiviral agent is questionable [73] . Syngouna (HTLV-1) using cadmium-tellurium quantum dots [90] . Similarly, Bentzen et al.

successfully utilized quantum dots to identify the presence of RSV and also monitor their progression infection over time [91] .

When the size of the therapeutic compound is very large, then INPs might not have promising effects. In this case, organic nanoparticles (ONPs) might prove effective treatment [92] . The following organic nanoparticles are investigated to be effective for treating viral infections like NIPAH virus.

These nanoparticles are effective against HIV [93] , Influenza A virus, and NiV [94] . 

PLGA, a degradable polymer that has been used in many FDA approved devices, has long been the standard NP material for intravaginal delivery of therapeutics [101] . HIV uses the brain as a reservoir for infection; hence, it is a likely target to fight this pathology. As most drug therapies (e.g. efavirenz) cannot cross BBB barriers, PLGA based nanoparticles can serve as carriers to the brain [96] . Other protease inhibitors (PIs) have also been extensively 

The 

Salts form of alginic acid is one of the most widely considered polymers in drug delivery applications [106] . Because its biocompatibility, nontoxicity, and quick elimination from the body make its application in the development of drug delivery systems [107] . In a separate study, amide functionalized alginate nanoparticles (AZT-GAAD NPs) were encapsulated J o u r n a l P r e -p r o o f with zidovudine (AZT) by emulsion solvent evaporation method. The novelty of this study was the absence of chemical cross-linking agents for the preparation of nanoparticles. The results suggested that alginate nanoparticle is a capable delivery vector for effective antiviral drug delivery and particularly for HIV/AIDS therapy. Figure 4D 

Chitosan is a well-known polymer with favorable features such as biocompatibility, biodegradability, nontoxic polysaccharide with mucoadhesive properties, and nonimmunogenicity, having significance in many fields of study [108] [109] [110] . HIV-1 inhibitor peptide derived from GB virus C was loaded in a novel polymeric NPs covered with glycolchitosan [111] . Further, the nanoparticle was confined to upper-layer epithelial mucosa and 

PCL is a synthetic polyester that is partially crystalline, having a low melting point ( [116] . Similarly, polyanhydride nanoparticles encapsulating inactivated swine influenza A virus (SwIAV) vaccine was assessed to induce protective immunity against a heterologous IAV challenge in pigs [117] . Poultry industries are also affected by viral disease conditions, for instance Newcastle disease (ND), a serious disease that threatens them in many countries, and no treatments available until date. The vaccine against Newcastle disease virus (NDV) encapsulated in nanoparticles was widely used due to their proven high safety, induced quicker, better mucosal, and humoral immune responses. These studies provide a direction for using the biodegradable materials to research and develop the targeted nano-formulated human vaccines [118] .

Despite a few limitations, lipid-based nanoparticles have antiviral activity against HIV [119] [106], Human papillomavirus [120] , other viruses like HCV and NiV. Commonly used lipidbased nanoparticles contain liposomes and solid lipid nanoparticles (SLN). Liposomes are spherical colloidal particles prepared using one or more concentric lipid bilayers composed of J o u r n a l P r e -p r o o f phospholipids and cholesterol molecules encapsulating an aqueous reservoir [121] . The liposome size varies between nm-µm. There are three types of liposomes [122] , liposomes multilamellar, MLV (multilamellar vesicles), relatively stable but polydisperse (100 nm to 10 µm); small unilamellar liposomes, SUVs (small unilamellar vesicles) of narrower size distribution (30 to 50 nm), but less stable and of low capacity; the third type of liposome, the LUVs (large unilamellar vesicles) of average diameter varying between 0.1 to 1 µm, larger capacity. Since the last few decades, these particles have been used as tools for biology and biochemistry as carriers of therapeutic and imaging agents [122, 123] . The principl hydrophobic or hydrophilic active agents can be loaded respectively in the bilayers lipid or the aqueous compartment. Their non-toxic and biocompatible character makes these colloids interesting systems for in vivo applications [124] . However, liposomes also have some limitations: they actually showed a low encapsulation capacity (especially for lipophilic molecules trapped in the phospholipid double layer), stability moderate and early release of hydrophilic active agents into the blood [125] . SLNs are structured around a lipid core, generally based on biodegradable triglycerides, bioassimilable and non-toxic [126] . The size of these particles varies between 50 nm and 1 µm. The heart of these particles developed during the 1990s consists of a lipid matrix that is solid at room temperature but also at the temperature of the human body. This matrix more or less crystallized is stabilized by a layer Vi amin E (α-tocopherol) was successfully used for targeted drug delivery systems to deliver the siRNAs from the serum to the liver [127] . Cholesterol-based cationic liposomes was conjugated to vitamin E and used to deliver inhibitory siRNA specifically to the liver in mouse models which led to suppression in both HCV core antigen production and firefly luciferase activity [127] (used as a reporter gene to determine extent of HCV replication) 

Dendrimers are organic compounds which have proven effect against Influenza virus, EBOV, zika virus, HSV, NiV and HIV due to inhibition of viral entry and activation of CD8+ T cells [130] [131] [132] . However, their action against NiV is yet to be evaluated. Niosomes are also effective against HSV [133] . Dendrimers are highly branched macromolecules perfectly monodisperse [134] . This strong branching of the polymer molecules gives the dendrimers of different chemical and physical properties of polymer molecules linear, which are of great interest for biomedical and industrial applications. Dendrimers can be synthesized by divergent and convergent methods. In divergent methods [135] , the dendrimer grows outwardly from the basic molecule. Monomer containing one reactive group and two dormant J o u r n a l P r e -p r o o f groups reacts first with the nucleus forming the first generation dendrimer, and successively, the new rim of the molecule is activated and reacts with several monomers until a large macromolecular structure is formed. This process has the drawbacks that the by-products formed are not easy to purify. In the methods convergent [136] , the dendrimer is synthesized in stages from the exterior groups. When branched molecules are large enough, they are attached to a molecule core. The dendrimers generated by these methods are easy to purify and have a structure controlled. Dendrimers have already been used as contrast agents for imaging by magnetic resonance [137] , as drug delivery systems [138] , as therapeutic agents by boron neutron capture [139] , in gene therapy as as vectors of gene transfer across the cell membrane [140] , and in medicine regenerative [141] .

Analogously to amphiphilic lipids, the di-block copolymers, with a block hydrophilic and a hydrophobic block, form micelles in some solvents. An excellent example of the use of block copolymer micelles as nanovectors targeted for therapeutic delivery are micelles formed by the block polymer. Polylactic, polymethoxy ethylene glycol, and folate-poly (ethylene glycol) of a diameter of 146 nm developed by Zhu et al. [142] . Polymersomes are artificial vesicles similar in structure to vesicles lipidic, but based on amphiphilic block copolymers [143] .

They can be prepared by the same methods as those used for lipid vesicles and liposomes.

The preparation methods can be summarized in two groups: techniques without solvent and solvent displacement techniques [144] . Solvent-free techniques consist of the hydration of the block copolymer in the dry state to form vesicles, for example, rehydration of the polymeric film [145] or electroforming [146] . The last method consists of the rehydration of polymers distributed over a pair of electrodes; once the solvent is added, an electric field is applied to facilitate hydration and formation of vesicles. Solvent displacement techniques are methods J o u r n a l P r e -p r o o f that require a first step to dissolve the block copolymer in an organic solvent before mixing with some water. After mixing, the organic solvent is removed by various methods. The injection process [147] , reverse phase evaporation [148, 149] and depletion of detergent [150] are examples of solvent displacement techniques used for polymers. Polymersomes are very attractive due to their structural similarity to biological membranes. Compared to lipid vesicles and liposomes, polymersomes have the advantage of forming flexible structures, high mechanical stability and resistance to an external stimulus [151] . Polymersomes can encapsulate hydrophobic or hydrophilic molecules. They can be used as nanovectors for administration of therapeutic agents.

Nano micelles are effective antiviral particles mostly due to encapsulation, biocompatibility, colloidal stability, and prolonged circulation time [152] . J o u r n a l P r e -p r o o f

Like other viral infections, there is a possibility of utilizing nanotechnology for treating the EBOV. Some of the particles include inorganic particles like silica and carbon-based nanocarriers [77, 78] , and organic particles like dendrimers [130] and hybrid particles [153] .

Humans' infection by lethal pathogens such as Ebola and other related viruses has not been properly addressed so far [155] . EBOV is one of the lethal viruses causing infection in humans. Numerous epidemics have been reported, mainly in Central Africa, ever since its initial description in 1976 in Zaire (now the Democratic Republic of the Congo). Zaire EBOV species within the EBOV genus of the family Filoviridae, in which three additional varieties of highly pathogenic agents Sudan, Tai Forest, and Bundibugyo viruses have also been described [156] . EBOV is communicated by direct contact with the body fluids of infected persons and objects contaminated with virus or infected animals [157] . WHO has accredited Ebola as a widespread public health emergency of international concern with severe global economic issues. The recent outbreaks of EBOV in West Africa underscore the urgent need to develop an effective EBOV vaccine [158] . While a variety of therapeutics strip (Nanozyme-strip), detecting the glycoprotein of EBOV as low as 1 ng/mL, which is 100-fold more sensitive than the standard strip method [160] . Nanozyme-strip test can rapidly and sensitively detect EBOV, providing a valuable simple screening tool for diagnosis of infection in Ebola-stricken areas.

Although the nanotechnology-based approaches for the managing of emerging and re- Another challenge is that the viruses may have numerous reservoirs over the time that make the therapy difficult [7] . In the future, the antiviral diseases such as COVID-19 will be managed by developing of nanotheranostic approaches which not only diagnose the early stage of viral infection, but also will be useful for the treatment of viral infections [6] .

This review has explored the application of various nanoparticles in the diagnosis and treatment of emerging and re-emerging viruses in general. Different nanotechnological approaches have shown the ability to improve the efficacy against viruses while reducing their toxicity. The development of nanotechnology-based antiviral delivery systems is a potential strategy to improve the efficacy and safety of current therapy. The use of nanoparticles as adjuvants for vaccines has also produced interesting results, which contribute to the development of an efficient and safe anti-viral vaccine design. This comprehensive review offers insight into nano no og ' remarkable potential in effective diagnosis, prevention, and treatment with a particular focus on the recently emerged virus COVID -19.

The authors report no conflicts of interest in this work. with AuNPs, the adsorption step is blocked by the binding of AuNPs and the viral envelope; therefore, the infection cannot be initiated [65] . Negatively charged GO has more chances to interact with the positively charged viruses, leading to virus damage and the inhibition of infection. c) Infection was blocked by GO conjugated with nonionic PVP but d) not with cationic PDDA [81] ; C) Schematic representation of the antiviral activity of derivatives of maximin bound to fullerene C60 nanocrystals against bacteriophage k as a model virus [82] ; D) Schematic representation of the antiviral activity of self-assembled glycodendro [60] fullerene monoadducts against Ebola virus glycoprotein pseudotyped viral particles on Jurkat cells overexpressing DC-SIGN [84] ; E) Schematic structure of a decorated carbon dot with EDA and EPA [86] . [63] ; B) Schematic illustration of inactivation of influenza virus treated with porous AuNPs which interact with virus surface proteins and cleave their disulfide bonds [64] ; C) Schematic representation of a proposed mode of the virucidal effect of AuNPs on Measles virus infection. In cells treated with AuNPs, the adsorption step is blocked by the binding of AuNPs and the viral envelope; therefore, the infection cannot be initiated [65] . [79] ; B) Proposed mechanisms of the antiviral activity of GO. a) Normal viruses are absorbed into cells by interacting with cell receptors to initiate infection. b) Negatively charged GO has more chances to interact with the positively charged viruses, leading to virus damage and the inhibition of infection. c) Infection was blocked by GO conjugated with nonionic PVP but d) not with cationic PDDA [81] ; C) Schematic representation of the antiviral activity of derivatives of maximin bound to fullerene C60 nanocrystals against bacteriophage k as a model virus [82] ; D) Schematic representation of the antiviral activity of self-assembled glycodendro [60] fullerene monoadducts against Ebola virus glycoprotein pseudotyped viral particles on Jurkat cells overexpressing DC-SIGN [84] ; E) Schematic structure of a decorated carbon dot with EDA and EPA [86] . 

Coronavirus susceptibility to the antiviral remdesivir (GS5734) is mediated by the viral polymerase and the proofreading exoribonuclease

Nipah virus contamination of hospital surfaces during outbreaks

Nipah virus infection: current scenario

A human lung xenograft mouse model of Nipah virus infection

Comparison of the pathogenicity of Nipah virus isolates from Bangladesh and Malaysia in the Syrian Hamster

Nanomedicine for the SARS-CoV-2: State-of-the-Art and Future Prospects

Manipulative magnetic nanomedicine: the future of COVID-19 pandemic/endemic therapy

Nanoenabled biosensing systems for intelligent healthcare: towards COVID-19 management

Aspects of Pointof-Care Diagnostics for Personalized Health Wellness

Grand Challenges in Bio-Nanotechnology to Manage the COVID-19 Pandemic

Electrochemical SARS-CoV-2 Sensing at Point-of-Care and Artificial Intelligence for Intelligent

Emerging Therapeutic Approaches to Combat COVID-19: Present Status and Future Perspectives

Anti-HIV-1 nanotherapeutics: promises and challenges for the future

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

HIV infection of naturally occurring and genetically reprogrammed human regulatory Tcells

HIV Infection Deregulates the Balance Between Regulatory T Cells and IL-2-Producing CD4 T Cells by Decreasing the Expression of the IL-2 Receptor in Treg

Human regulatory T cells are targets for human immunodeficiency Virus (HIV) infection, and their susceptibility differs depending on the HIV type 1 strain

Nanotechnology as a new therapeutic approach to prevent the HIV-infection of Treg cells

Potential inhibition of HIV-1 encapsidation by oligoribonucleotide-dendrimer nanoparticle complexes

Sustained-release nanoART formulation for the treatment of neuroAIDS

Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy

Nanoparticlebased ARV drug combinations for synergistic inhibition of cell-free and cell-cell HIV transmission

Functional Carbon Quantum Dots as Medical Countermeasures to Human Coronavirus

Targeting dendritic cells through gold nanoparticles: a review on the cellular uptake and subsequent immunological proper ties

Nanoparticle vaccines against infectious diseases

Immunological properties of gold nanoparticles

Nucleoside and nucleotide HIV reverse transcriptase inhibitors: 25 years after zidovudine

Non-nucleoside reverse transcriptase inhibitors (NNRTIs), their discovery, development, and use in the treatment of HIV-1 infection: a review of the last 20 years

HIV-protease inhibitors

Discovery and optimization of a natural HIV-1 entry inhibitor targeting the gp41 fusion peptide

Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1

Highly active antiretroviral therapy: current state of the art, new agents and their pharmacological interactions useful for improving therapeutic outcome

Current status and challenges of antiretroviral research and therapy

Emerging nanotechnology approaches for HIV/ AIDS treatment and prevention

Anti-HIV-1 nanotherapeutics: promises and challenges for the future

Glycosystems in nanotechnology: gold glyconanoparticles as carrier for anti-HIV prodrugs

HIV infection of naturally occurring and genetically reprogrammed human regulatory T-cells

Human regulatory T cells are targets for human immunodeficiency virus (HIV) infection, and their susceptibility differs depending on the HIV type 1 strain

HIV infection deregulates the balance between regulatory T cells and IL-2-producing CD4 T cells by decreasing the expression of the IL-2 receptor in Treg

Nanotechnology as a new therapeutic approach to prevent the HIV-infection of Treg cells

Potential inhibition of HIV-1 encapsidation by oligoribonucleotide-dendrimer nanoparticle complexes

Sustained-release nanoART formulation for the treatment of neuroAIDS

Activation of HIV transcription with short course vorinostat in HIV-infected patients on suppressive antiretroviral therapy

Nanoparticle-based ARV drug combinations for synergistic inhibition of cell-free and cell-cell HIV transmission

A nanoparticle encapsulated non-nucleoside reverse transcriptase inhibitor with enhanced 1anti-HIV-1 activity and prolonged circulation time in plasma

Mechanism of multivalent nanoparticle encounter with HIV-1 for potency enhancement of peptide triazole virus inactivation

Activation of HIV-1 with nanoparticle-packaged small molecule protein phosphatase-1-targeting compound

Nano-based approach to combat emerging viral (NIPAH virus) infection

Chapter 14 -Nanoparticles in Antiviral Therapy

Metal nanoparticles: The protective nanoshield against virus infection

Biological activity of green-synthesized silver nanoparticles depends on the applied natural extracts: a comprehensive study

Antiviral properties of silver nanoparticles against norovirus surrogates and their efficacy in coated polyhydroxyalkanoates systems. LWT -Food Science and Technology

Cytotoxicity and antiviral activity of electrochemical -synthesized silver nanoparticles against poliovirus

Ultra-sonication-assisted silver nanoparticles using Panax ginseng root extract and their anti-cancer and antiviral activities

Antiviral and Immunomodulatory Activity of Silver Nanoparticles in Experimental RSV Infection

Tannic acid modified silver nanoparticles show antiviral activity in herpes simplex virus type 2 infection

Silver nanoparticles enhance survival of white spot syndrome virus infected Penaeus vannamei shrimps by activation of its immunological system

Gold nanoparticles as an HIV entry inhibitor

Gold nanoparticles impair foot-and-mouth disease virus replication

Detection of influenza virus using peroxidase-mimic of gold nanoparticles

Highly monodispersed gold nanoparticles synthesis and inhibition of herpes simplex virus infections

Gold nanorods inhibit respiratory syncytial virus by stimulating the innate immune response

Gold nanoparticles capped with sulfate-ended ligands as anti-HIV agents

Porous gold nanoparticles for attenuating infectivity of influenza A virus

Virucidal Activity of Gold Nanoparticles Synthesized by Green Chemistry Using Garlic Extract

Aptamer-conjugated magnetic nanoparticles for the efficient removal of HCV particles from human plasma samples

Highly sensitive, engineered magnetic nanosensors to investigate the ambiguous activity of Zika virus and binding receptors

Iron oxide nanoparticles based antiviral activity of H1N1 influenza A virus

Green synthesis of nanometal impregnated biomass -antiviral potential

Antiviral properties of silver nanoparticles on a magnetic hybrid colloid

Inactivation of MS2 bacteriophage by titanium dioxide nanoparticles in the presence of quartz sand with and without ambient light

Interaction of titanium dioxide nanoparticles with influenza virus

Critical review of the safety assessment of titanium dioxide additives in food

Photocatalytic inactivation of viruses using titanium dioxide nanoparticles and low-pressure UV light

ina i a ion o p ag MS2, ΦX174 and R772 ing UV and solar photocatalysis

Viral inhibition mechanism mediated by surfacemodified silica nanoparticles

Antiviral activity of fullerene C60 nanocrystals modifiedwith derivatives of anionic antimicrobial peptide maximin H5

Synergistic antiviral effect of curcumin functionalized graphene oxide against respiratory syncytial virus infection

GAG mimetic functionalised solid and mesoporous silica nanoparticles as viral entry inhibitors of herpes simplex type 1 and type 2 viruses

Silica nanoparticles as the adjuvant for the immunisation of mice using hepatitis B core virus-like particles

Antiviral Activity of Graphene Oxide: How Sharp Edged Structure and Charge Matter

Antiviral activity of fullerene C60 nanocrystals modified with derivatives of anionic antimicrobial peptide maximin H5. Monatshefte für Chemie -Chemical Monthly

Fullerene Derivatives Strongly Inhibit HIV-1 Replication by Affecting Virus Maturation without Impairing Protease Activity

Antiviral activity of self-assembled glycodendro[60]fullerene monoadducts

Carbon dots as inhibitors of virus by activation of type I interferon response

Quantum Dots and Their Multimodal Applications: A Review

Core-shell quantum dots: Properties and applications

Enhancing the delivery of anti retroviral drug "Saquinavir" across the blood brain barrier using nanoparticles

Quantum Dot-Based Biosensor for the Detection of Human T-Lymphotropic Virus-1

Progression of respiratory syncytial virus infection monitored by fluorescent quantum dot probes

Organic nanoparticles for drug delivery and imaging

Gelatin modified lipid nanoparticles for anti-viral drug delivery

Double-layered protein nanoparticles induce broad protection against divergent influenza A viruses

Molecularly Imprinted Polymer Nanoparticles as Potential Synthetic Antibodies for Immunoprotection against HIV

Polymeric nanoparticles for enhancing antiretroviral drug therapy

Development and characterization of a long-acting nanoformulated abacavir prodrug

Evaluation of chitosan nanoformulations as potent anti-HIV therapeutic systems

Encapsulation of zidovudine in PF-68 coated alginate conjugate nanoparticles for anti-HIV drug delivery

Oral delivery of indinavir using mPEG-PCL nanoparticles: preparation, optimization, cellular uptake, transport and pharmacokinetic evaluation

Degradable bioadhesive nanoparticles for prolonged intravaginal delivery and retention of elvitegravir

Liver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication

Mannose-Modified PLGA Nanoparticles for Sustained and Targeted Delivery in Hepatitis B Virus Immunoprophylaxis

Polymeric nanoparticles containing combination antiretroviral drugs for HIV type 1 treatment

Physical approaches to biomaterial design

Nanovehicular intracellular delivery systems

Protein release from alginate matrices

Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses

Optimization of chitosan nanoparticles as an anti-HIV siRNA delivery vehicle

Inhibiting influenza virus replication and inducing protection against lethal influenza virus challenge through chitosan nanoparticles loaded by siRNA

Penetration of polymeric nanoparticles loaded with an HIV-1 inhibitor peptide derived from GB virus C in a vaginal mucosa model

Development and characterization of chitosan coated poly-(ɛ-caprolactone) nanoparticulate system for effective immunization against influenza

32 -Biodegradation of Biopolymers

Biodegradable poly(epsilon -caprolactone) nanoparticles for tumor-targeted delivery of tamoxifen

Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine

Enhanced antiviral activity of Acyclovir loaded into beta-cyclodextrin-poly(4-acryloylmorpholine) conjugate nanoparticles

Polyanhydride nanovaccine against swine influenza virus in pigs

Newcastle disease virus vaccine encapsulated in biodegradable nanoparticles for mucosal delivery of a human vaccine

Poly (vinyl pyrrolidone)-lipid based hybrid nanoparticles for anti viral drug delivery

Development of podophyllotoxinloaded nanostructured lipid carriers for the treatment of condyloma acuminatum

Multifunctional nanocarriers

Liposome as a drug carrier system: Prospects for safer prescribing during pregnancy: A review

The carrier potential of liposomes in biology and medicine (second of two parts)

Pharmacokinetics of pegylated liposomal Doxorubicin: review of animal and human studies

Targeted delivery of antibiotics using liposomes and nanoparticles: research and applications

Solid lipid nanoparticles: a modern formulation approach in drug delivery system

Target delivery of small interfering RNAs with vitamin E-coupled nanoparticles for treating hepatitis C

Production of infectious hepatitis C virus in tissue culture from a cloned viral genome

Controlling HBV Replication in Vivo by Intravenous Administration of Triggered PEGylated siRNA-Nanoparticles

Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose

Evaluation of G2 citric acid-based dendrimer as an adjuvant in veterinary rabies vaccine

An RNA nanoparticle vaccine against Zika virus elicits antibody and CD8+ T cell responses in a mouse model

Preparation and evaluation of the antiviral activity of acyclovir loaded nano-niosomes against herpes simplex virus type 1 Pharmaphore

Novel Hollow Polymer Shells by Colloid-Templated Assembly of Polyelectrolytes

Nanoengineering of inorganic and hybrid hollow spheres by colloidal templating

Defoliation and Plasmid Delivery with Layer-by-Layer Coated Colloids

The Decomposition Process of Melamine Formaldehyde Cores: The Key Step in the Fabrication of Ultrathin Polyelectrolyte Multilayer Capsules

Melamine Formaldehyde Core Decomposition as the Key Step Controlling Capsule Integrity: Optimizing the Polyelectrolyte Capsule Fabrication

Microencapsulation of Uncharged Low Molecular Weight Organic Materials by Polyelectrolyte Multilayer Self-Assembly

Cross-Linked, Luminescent Spherical Colloidal and Hollow-Shell Particles

Mesoporous Silica Particles as Templates for Preparing Enzyme-Loaded Biocompatible Microcapsules

Dendrimers and their applications in immunoassays and clinical diagnostics

Macromolecular MRI contrast agents with small dendrimers: pharmacokinetic differences between sizes and cores

Dendrimers and dendritic polymers in drug delivery

Site-specific conjugation of boron-containing dendrimers to anti-EGF receptor monoclonal antibody cetuximab (IMC-C225) and its evaluation as a potential delivery agent for neutron capture therapy

Dendrimers in gene delivery

Dendrimers and derivatives as a potential therapeutic tool in regenerative medicine strategies-A review

Enhancement of entrapping ability of dendrimers by a cubic silsesquioxane core

Nanocatalysts based on dendrimers

Direct Synthesis of Polymer Nanocapsules: Self-Assembly of Polymer Hollow Spheres through Irreversible Covalent Bond Formation

Nanoencapsulation I. Methods for preparation of drug-loaded polymeric nanoparticles

Corecrosslinked polymeric micelles: principles, preparation, biomedical applications and clinical translation

Site-specific targeting of enterovirus capsid by functionalized monodisperse gold nanoclusters

An integrated vitamin E-coated polymer hybrid nanoplatform: A lucrative option for an enhanced in vitro macrophage retention for an anti-hepatitis B therapeutic prospect

Multivalent Glycosylated Nanostructures To Inhibit Ebola Virus Infection

Proposal for a revised taxonomy of the family Filoviridae: classification, names of taxa and viruses, and virus abbreviations

Towards detection and diagnosis of Ebola virus disease at point-of-care

Vaccine nanoparticles displaying recombinant Ebola virus glycoprotein for induction of potent antibody and polyfunctional T cell responses

Ultrasensitive Ebola Virus Detection Based on Electroluminescent Nanospheres and Immunomagnetic Separation

Nanozyme-strip for rapid local diagnosis of Ebola

C) Antiviral effect of phytosynthesized AgNPs on MDCK cells (A/PR/8 virus-infected) by SRB assay at 24 h

D) Schematic representation of the interaction between tannic acid modified AgNPs or tannic acid and HSV-2 virion

Figure 1 A) Potential antiviral mechanism of AgNPs. (1) AgNPs interact with viral envelope and/or viral surface proteins; (2) AgNPs interact with cell membranes and block viral penetration; (3) AgNPs block cellular pathways of viral entry; (4) AgNPs interact with viral genome; (5) AgNPs interact with viral factors necessary for viral replication; (6) AgNPs interact with cellular factors necessary for productive viral replication

Killer activity of untreated, b) C-AgNP-treated, c) GT-AgNP-treated Saccharomyces cerevisiae SZMC 20733 cells. Numbers (1-5) indicate the colonies of C-AgNP-treated cells where no killer phenotype was observed, whereas GT-AgNP-treated colonies with lost killer activity are indicated with black arrows, d) Killer phenotype of Saccharomyces cerevisiae SZMC 20733 (K) and C-AgNPtreated strains (1-5) after ~112 generations, and e) Viral RNA extracted from SZMC 20733 (K) and from C-AgNP-treated strains (1-5)

C) Antiviral effect of phytosynthesized AgNPs on MDCK cells (A/PR/8 virus-infected) by SRB assay at 24 h

D) Schematic representation of the interaction between tannic acid modified AgNPs or tannic acid and HSV-2 virion