COVID-19: Characteristics and Therapeutics

Abstract

Novel coronavirus (COVID-19 or 2019-nCoV or SARS-CoV-2), which suddenly emerged in December 2019 is still haunting the entire human race and has affected not only the healthcare system but also the global socioeconomic balances. COVID-19 was quickly designated as a global pandemic by the World Health Organization as there have been about 98.0 million confirmed cases and about 2.0 million confirmed deaths, as of January 2021. Although, our understanding of COVID-19 has significantly increased since its outbreak, and multiple treatment approaches and pharmacological interventions have been tested or are currently under development to mitigate its risk-factors. Recently, some vaccine candidates showed around 95% clinical efficacy, and now receiving emergency use approvals in different countries. US FDA recently approved BNT162 and mRNA-1273 vaccines developed by Pfizer/BioNTech and Moderna Inc. for emergency use and vaccination in the USA. In this review, we present a succinct overview of the SARS-CoV-2 virus structure, molecular mechanisms of infection, COVID-19 epidemiology, diagnosis, and clinical manifestations. We also systematize different treatment strategies and clinical trials initiated after the pandemic outbreak, based on viral infection and replication mechanisms. Additionally, we reviewed the novel pharmacological intervention approaches and vaccine development strategies against COVID-19. We speculate that the current pandemic emergency will trigger detailed studies of coronaviruses, their mechanism of infection, development of systematic drug repurposing approaches, and novel drug discoveries for current and future pandemic outbreaks.

Keywords: COVID-19; SARS-CoV-2; coronavirus; epidemiology; pandemic; spike protein; therapeutics; vaccine.

Figure 1

Structure and genomic organization of SARS-CoV-2. (A) Schematic representation of SARS-CoV-2 virus structure and the positions of spike glycoprotein, hemagglutinin-esterase, envelope, membrane, nucleocapsid, and RNA viral genome. (B) Genomic organization of SARS-CoV-2 representing ORF1a, ORF1B which encode for nonstructural proteins such as papain-like protease, 3CL-protease, RNA-dependent RNA polymerase, helicase, and endoribonuclease. Genes coding for spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins are also displayed. Ribosomal frameshift location between ORF1 and ORF2 is shown at the junction of ORF1/2. Genomic positions are shown with dashed lines followed by nucleotide position number in RNA viral genome. The box highlights the genomic organization of spike (S) gene showing distinct S1 and S2 subunits coding segments. (C) Schematic magnified representation of SARS-CoV-2 spike glycoprotein showing S1 and S2 subunits. (D) Crystallographic structure of SARS-CoV-2 spike glycoprotein adapted from PDB ID:6VXX. Receptor binding domain (RBD) representing ACE2 receptor binding site in human cells, N-terminal domain (NTD), fusion protein (FP), transmembrane anchor (T.A.), and intracellular tail (I.T.) protein domains are displayed.

Figure 2

Schematic representation of SARS-CoV-2 virus life cycle. Drugs targeting different steps of coronavirus entry and lifecycle in human cells are also shown.

Figure 3

Schematic representation of some ongoing strategies for SARS-CoV-2 vaccine and their respective mechanism of action.