A Review on SARS-CoV-2 Virology, Pathophysiology, Animal Models, and Anti-Viral Interventions

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective antiviral therapy or vaccine currently exists, and supportive care remains to be the cornerstone treatment. Through previous lessons learned from SARS-CoV-1 and MERS-CoV studies, scientific groups worldwide have rapidly expanded the knowledge pertaining to SARS-CoV-2 virology that includes in vitro and in vivo models for testing of antiviral therapies and randomized clinical trials. In the present narrative, we review SARS-CoV-2 virology, clinical features, pathophysiology, and animal models with a specific focus on the antiviral and adjunctive therapies currently being tested or that require testing in animal models and randomized clinical trials.

Keywords: COVID-19; SARS-CoV-2; animal models; antivirals.

Figure 1

Schematic illustration of SARS-CoV-2-S; RBD: receptor binding domain; RBM: receptor binding motif; TD: transmembrane domain. Polybasic or alternative cleavage site (S1/S2), and TMPRSS2 or Cathepsin B/L (S2’) cleavage site are indicated in vertical solid and dashed lines, respectively. Amino acid sequences surrounding the protease recognition sites are indicated in red and protease cleavage site is denoted by an asterisk*.

Figure 2

Genomic organization of SARS-CoV-2.

Figure 3

Schematic illustration of steps of virus replication and virus-induced host immune response targeted by various therapies under investigation. ACE2: angiotensin-converting enzyme 2; TMPRSS2: type 2 transmembrane serine protease; NHC: β-D-N4-hydroxycytidine; vRdRp: viral RNA dependent RNA polymerase; HHT: Homoharringtonine; and IFN: interferon.