Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach

Biochim Biophys Acta Mol Basis Dis. 2020 Oct 1;1866(10):165878. doi: 10.1016/j.bbadis.2020.165878. Epub 2020 Jun 13.


The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present study highlights the genomic, proteomic, pathogenesis, and therapeutic strategies in SARS-CoV-2 infection. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins has been performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, which makes available drugs ineffective.

Keywords: COVID-19; Comparative genomics; Drug target; Molecular basis of pathogenesis; Molecular evolution; SARS-CoV-2.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Betacoronavirus / genetics*
  • Betacoronavirus / isolation & purification
  • Betacoronavirus / pathogenicity
  • COVID-19
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / pathology
  • Coronavirus Infections / virology
  • Cytokines / metabolism
  • Genetic Variation
  • Genome, Viral*
  • Humans
  • Middle East Respiratory Syndrome Coronavirus / genetics
  • Middle East Respiratory Syndrome Coronavirus / isolation & purification
  • Middle East Respiratory Syndrome Coronavirus / pathogenicity
  • Pandemics
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / pathology
  • Pneumonia, Viral / virology
  • RNA-Dependent RNA Polymerase / genetics
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / chemistry


  • Cytokines
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • RNA-Dependent RNA Polymerase