Potential drug targets of SARS-CoV-2: From genomics to therapeutics

Int J Biol Macromol. 2021 Apr 30:177:1-9. doi: 10.1016/j.ijbiomac.2021.02.071. Epub 2021 Feb 9.

Abstract

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from China has become a global threat due to the continuous rise in cases of Coronavirus disease 2019 (COVID-19). The problem with COVID-19 therapeutics is due to complexity of the mechanism of the pathogenesis of this virus. In this review, an extensive analysis of genome architecture and mode of pathogenesis of SARS-CoV-2 with an emphasis on therapeutic approaches is performed. SARS-CoV-2 genome consists of a single, ~29.9 kb long RNA having significant sequence similarity to BAT-CoV, SARS-CoV and MERS-CoV genome. Two-third part of SARS-Cov-2 genome comprises of ORF (ORF1ab) resulting in the formation of 2 polyproteins, pp1a and pp1ab, later processed into 16 smaller non-structural proteins (NSPs). The four major structural proteins of SARS-CoV-2 are the spike surface glycoprotein (S), a small envelope (E), membrane (M), and nucleocapsid (N) proteins. S protein helps in receptor binding and membrane fusion and hence plays the most important role in the transmission of CoVs. Priming of S protein is done by serine 2 transmembrane protease and thus plays a key role in virus and host cell fusion. This review highlights the possible mechanism of action of SARS-CoV-2 to search for possible therapeutic options.

Keywords: Coronavirus disease 19; Drug targets; Severe acute respiratory syndrome coronavirus-2.

Publication types

  • Review

MeSH terms

  • COVID-19 Drug Treatment*
  • Coronavirus RNA-Dependent RNA Polymerase / chemistry
  • Coronavirus RNA-Dependent RNA Polymerase / metabolism
  • Genome, Viral*
  • Humans
  • Nucleocapsid Proteins / chemistry
  • Nucleocapsid Proteins / metabolism
  • Peptide Hydrolases / metabolism
  • SARS-CoV-2 / chemistry
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / physiology
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / metabolism
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / metabolism

Substances

  • Nucleocapsid Proteins
  • Viral Envelope Proteins
  • Viral Nonstructural Proteins
  • Coronavirus RNA-Dependent RNA Polymerase
  • Peptide Hydrolases