Mon. Dec 6th, 2021

A recent review article looks at the potential of nanotechnology to combat severe acute respiratory syndrome 2 (SARS-CoV-2), with several options for strategies in therapy, vaccines, and prevention.

The review article, published in the journal Nanomaterials provides insight into recent studies using metal nanocomposites as antiviral agents. In addition to discussing SARS-CoV, Middle Eastern Respiratory (MERS) CoV, and coronavirus, other envelope and RNA viruses are also included as targets for metallic nanomaterials in this review.

Study: Metal Nanoparticles Against Viruses: Opportunities to Fight SARS-CoV.  Image credit: Georgy Shafeev / Shutterstock

Introduction

The new coronavirus, SARS-CoV-2, which appeared in late December 2019 in Wuhan, China, is responsible for coronavirus disease 2019 (COVID-19). Belongs to Coronaviridae family, seven viruses are capable of infecting humans: human coronavirus 229E (HCoV-229E) and human coronavirus NL63 (HCoV-NL63), (belongs to the genus Alfacoronavirus), and human coronavirus OC43 (HCoV-OC43), human coronavirus HKU1 (HCoV-HKU1), Middle East Respiratory Virus (MERS-CoV), SARS-CoV and SARS-CoV-2 (genus Betacoronavirus).

Among these, SARS-CoV, MERS-CoV and SARS-CoV-2 cause severe respiratory disease with complex pathophysiology associated with multiple organ failure, sepsis and death. Despite a low mutation rate (compared to influenza virus), variants with increased transmissibility, increased severity, and reduced antibody neutralization for COVID-19 have been identified to emerge globally.

The versatility of nanocomposites and nanoparticles enables them to fight infections and prevent viruses, including VOCs, without selective toxicity and adverse effects. In addition, the fact that the virus uses the host cell machinery for its replication is crucial in developing an antiviral drug that does not harm the host.

Unique size, high surface-to-volume ratio, surface plasmon resonance and malleable optical absorption spectra of metallic nanoparticles are some of the benefits of using nanotechnology for antiviral strategies – bioconjugation, nanobarriers or drug stabilization, production of host reactive oxygen species (ROS), etc.

General human pathogenic coronavirus replication.  Attachment and entry through S-protein binding to specific host receptor.  Positive sense viral RNA released and polymerase translated.  Viral RNA is replicated and nucleocapsid (N) structural protein is synthesized in the cytoplasm, and S protein, membrane (M) and sheath (E) are transcribed / translated in the endoplasmic reticulum (ER) and transported to Golgi.  Viral components are packaged and assembled into a mature virion structure, which is then released

General human pathogenic coronavirus replication. Attachment and entry through S-protein binding to specific host receptor. Positive sense viral RNA released and polymerase translated. Viral RNA is replicated and nucleocapsid (N) structural protein is synthesized in the cytoplasm, and S protein, membrane (M) and sheath (E) are transcribed / translated in the endoplasmic reticulum (ER) and transported to Golgi. Viral components are packaged and assembled into a mature virion structure, which is then released

Metal nanoparticles as antiviral agents

Metal nanoparticles can attack multiple viral targets with minimal subsequent resistance development.

The best metal nanoparticles that are effective against bacteria and viruses are silver nanoparticles (AgNPs). The antiviral and inhibitory activity of AgNPs has been demonstrated against TGEV, porcine coronavirus, as a model for CoV and feline coronavirus (FCoV). AgNPs synthesized by curcumin were found to be less toxic than AgNPs than citric acid.

Graphene oxide (GO) has also been shown to be effective against coronavirus (swine fever diarrhea virus PEDV) and FCoV.

A complex of gold nanoparticles (AuNP) has been shown to interact with Dengue virus (DENV-2) envelope protein, permanently inhibiting the virus. Studies have also shown that porous AuNPs without surfactants reduced the infectivity of various influenza virus strains (H1N1, H3N2 and H9N2).

The reviewers presented various studies involving nanometallic materials such as antiviral agents and the proposed mechanisms of action.

Nanoparticulate delivery systems against viruses

Difficulties with common antiviral drugs include solubility, permeability and absorption, which affect the bioavailability of the drug. Nanoparticulate delivery systems for the bioactive compounds, immunogenic drugs or proteins, can overcome these challenges. Nanocarriers have been well studied and effective against HIV and dengue virus (DENV) with a cationic complex AuNP siRNA.

Because no known drug effectively interferes with SARS-CoV-2 replication, the reviewers have not directly addressed it as a drug nanocarrier for SARS-CoV-2.

Nanovaccinology

In the ongoing pandemic, vaccination has been the most effective medical intervention to control the infection. Nanoparticles are extensively explored as vaccine adjuvants, for example lipid-based and polymeric nanomaterials.

Conjugated 100 nm gold nanoparticles with S (tip) glycoprotein from avian coronavirus have elicited a robust immune response in mouse models.

A recent study suggested a vaccine that combines immune modulation of AuNPs, covered with antiviral polysaccharides and loaded with SARS-CoV-2 S or N (nucleocapsid) proteins.

Metallic nanoparticles in COVID-19 diagnosis

Combining diagnosis with the ability to tailor a metallic nanomaterial with specific properties can be a crucial weapon in the fight against COVID-19.

Currently, COVID-19 diagnosis can be performed based on viral sequences, patient antibodies, or SARS-CoV-2 antigens detected from nasopharyngeal or oropharyngeal inoculum samples from patients (the gold standard for sampling).

Likewise, magnetic nanoparticles are easy and efficient in SARS-CoV-2 detection through electrochemical, fluorescence or magnetic resonance properties. The magnetic particles can be used to extract SARS-CoV-2 RNA from samples and help increase the sensitivity of detection based on the amplification methods.

Metallic nanoparticles in personal protective equipment

Despite the rollout of vaccination, personal protective equipment (PPE) is mandatory to stop the viral spread via carriers. Reports showed anti-SARS-CoV-2 activity by incorporating metal nanoparticles into these PPEs. Various nanomaterials such as silver nanoparticles, copper oxide, iodine, titanium oxide are discussed for use in these PPE products.

Future perspectives

It is difficult to develop an antiviral drug for viruses that are mandatory intracellular parasites that rely on host cell machinery for replication, so nanotechnology may be a potential solution.

The tunable properties and proven potential of nanomaterials make them a promising alternative to current antiviral agents. The use of these tools can be used to prevent future epidemics and pandemics.

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