COVID-19: Unmasking Emerging SARS-CoV-2 Variants, Vaccines and Therapeutic Strategies

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, which has been a topic of major concern for global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta), which show increased transmissibility and resistance towards vaccines and therapies. Importantly, there is convincing evidence of increased susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response and comorbidities. Herein, we provide a comprehensive perspective regarding vulnerability of SARS-CoV-2 infection in patients with underlying medical comorbidities. We discuss ongoing vaccine (mRNA, protein-based, viral vector-based, etc.) and therapeutic (monoclonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail, the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.

Keywords: COVID-19; SARS-CoV-2; antibody; biomolecules; comorbidities; coronavirus; immune dysregulated; spike protein; vaccines; variants; variants of concern (VOC).

Figure 1

Timeline of major key events in the progression of the COVID-19 pandemic and vaccine development. Counts shown here are confirmed cases and deaths worldwide (https://ourworldindata.org/- Source- Johns Hopkins University CEES COVID-19 DATA, accessed date: 28 May 2021). CQ, Chloroquine; HCQ, Hydroxychloroquine; EUA, emergency use authorization.

Figure 2

Structural regions of SARS-CoV-2 involved in the pathogenicity. (A) SARS-CoV-2 genomic organization and structural components of spike (S) protein. The furin cleavage site (682–689 residues) at the junction of S1 and S2 subunit is critical to facilitate viral fusion and entry to host cells. (B) SARS-CoV-2 variants with identified mutation sites in the structural region. UTR, untranslated region; SP, signal peptide; FP, fusion peptide; HR, heptad repeat domain; TM, transmembrane domain; CP, cytoplasmic domain. UK, United Kingdom; SA, South Africa; US, United states. This figure was prepared using IBS 1.0.3 [31].