Nanoplatforms for COVID-19: Strategies, Prevention and Therapeutics

Abstract

The ongoing pandemic Coronavirus disease 2019 (COVID-19) is one of the highly infectious and transmissible disease of the decade, which has globally threatened the human health and economic growth. COVID-19 is an outbreak of unusual viral pneumonia with wide spectrum of clinical manifestations, which includes asymptomatic to severe illness with respiratory failure, multiorgan and systemic dysfunctions [1]. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which spread in late 2019 from Wuhan, China. SARS-COV-2 is enveloped positive-stranded RNA (+ssRNA) virus, belonging to the same Coronaviridae family and subgenus (betacoronavirus) as SARS virus, which caused SARS outbreak in 2003. Viral particle is 60-140 nm in size and packaged within a capsid formed of nucleocapsid and surrounded by an envelope that contains membrane (M), spike (S) and envelope (E) structural proteins [1-2]. N, M and E proteins are critical for assembly, production of β-coronavirus particles and viral pathogenicity [1]. S protein plays an important role in viral infection by binding with host receptor and mediates virus entry into host cells [1]. SARS-COV-2 is transmitted by coughing or sneezing of contaminated droplets either by direct contact or indirectly. Since the outbreak and rapid spread of COVID-19 from late December 2019, millions of deaths have been reported globally. Although, SARS-CoV-2 is known for causing severe respiratory tract infection but extrapulmonary organs and organ systems are also affected by COVID-19 [3].

Therapies including remdesivir (antiviral) in combination with baricitinib (a Janus kinase inhibitor); dexamethasone (a corticosteroid), casirivimab and imdevimab (a cocktail of two monoclonal antibodies), bamlanivimab (a monoclonal antibody therapy) and convalescent plasma have received regulatory approval on the basis of promising results [4-6]. In addition, vaccines viz. Pfizer/BioNtech Comirnaty, SII/Covishield and AstraZeneca/AZD1222, Janssen/Ad26.COV 2, Moderna COVID-19 vaccine (mRNA 1273), Sinopharm, Sinovac-CoronaVac are approved by the US Food and Drug Administration (FDA) and/or European Medicines Agency for mass vaccination worldwide [7]. Despite these global efforts, the treatment options for COVID-19 remain limited and do not exhibit great clinical benefits. Moreover, severe COVID-19 (20 %) patients require intensive care admission with respiratory support, which is challenging to provide [7]. The lack of specific treatment and respiratory support system collapses the healthcare systems worldwide, resulting in uncertain prevalence of infection. For effective interventions in therapeutics, researchers are racing to find a specific treatment to accelerate development of promising, clinically translatable therapeutics against various viral infections.

Over the past decades, nanotechnology has gained immense attention, owing to the applications in molecular diagnostics, therapeutics, delivery vehicles and vaccines, which are compelling and monetarily reasonable measures to control any pandemic [8]. Furthermore, nanotechnology overcomes the limitations of conventional drug dosage forms and traditional delivery systems viz. poor solubility, low stability, lower concentration at site of infection, poor bioavailability, shorter half-life and higher toxicity [9]. One of the powerful nano-antimicrobial agents is metallic nanoparticles (NPs) e.g. Ag-NPs and their nanocomposites. Nanocomposites of Au-NPs, Ag-NPs, ZnO-NPs, and ClO₂ NPs possess broad spectrum antiviral activity and are able to inhibit SARS-CoV-2, human H1N1 and avian H5N1 influenza viruses. These nanocomposites also can provide prophylactic effects against SARS-CoV-2 and other opportunistic microbial infections by oral gargling, nasal spray and nebulized inhalation [10]. Interestingly, in vitro study showed the ability of Ag-NPs to inhibit SARS-CoV-2 replication [11]. In vivo study, further demonstrated that mouthwash and nose rinse with Ag-NPs (brand name ARGOVIT^®) prevented SARS-CoV-2 contagion in health workers who were at high-risk for acquiring the infection because of working in vicinity of COVID-19 patients [11]. Hence, Ag-NPs were proposed for use in non-pharmaceutical public health interventions as mouthwash and nose rinse to reduce morbidity. Moreover, nanomaterial-based drug delivery system such as messenger ribonucleic acid (mRNA) encapsulated lipid-nanoparticles (LNPs) is currently available as Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines [12-13]. These mRNA vaccines developed by BioNTech/Pfizer and Moderna were reported to exhibit about 95% efficacy [12-13]. LNPs as delivery system provides stability to mRNA and is able to successfully deliver it to cells [12]. The self-adjuvant properties of mRNA-LNP vaccine can enhance the titre of the neutralizing antibody and provide superior protection from infection, thus, reducing the risk of developing COVID-19 for the vaccine recipients [13]. Nanomaterials provide efficient drug delivery system and also exhibit broad-spectrum antiviral activity via prevention of viral-host interactions and viral replication; these indeed revolutionize nanomedicine/ nanotechnology for designing novel and effective therapeutic interventions against COVID-19 (Fig.1).

 This review summarizes the current knowledge of clinical, epidemiological and pathological features of COVID-19. The review highlights the role of nanomaterials as inhibitors of rapidly spreading SARS-CoV-2 and their ability to function as delivery vehicles and adjuvants. It also discusses the recent nanomaterial based therapeutic strategies, which can be used for treatment and prevention of COVID-19. This review systematically combines the available knowledge on use of nanotechnology to combat COVID-19, with an aim to enable researchers to innovate and further transform knowledge into products, and prevent future disease outbreaks for benefit and protection of society.