Current understanding on molecular drug targets and emerging treatment strategy for novel coronavirus-19

Naunyn Schmiedebergs Arch Pharmacol. 2021 Jul;394(7):1383-1402. doi: 10.1007/s00210-021-02091-5. Epub 2021 May 7.

Abstract

SARS-CoV-2 is an enveloped positive-sense RNA virus, contain crown-like spikes on its surface, exceptional of large RNA genome, and a special replication machinery. Common symptoms of SARS-CoV-2 include cough, common cold, fever, sore throat, and a variety of severe acute respiratory disease (SARD) such as pneumonia. SARS-CoV-2 infects epithelial cells, T-cells, macrophages, and dendritic cells and also influences the production and implantation of pro-inflammatory cytokines and chemokines. Repurposing of various drugs during this emergency condition can reduce the rate of mortality as well as time and cost. Two druggable protein and enzyme targets have been selected in this review article due to their crucial role in the viral life cycle. The eukaryotic translation initiation factor (eIF4A), cyclophilin, nucleocapsid protein, spike protein, Angiotensin-converting enzyme 2 (ACE2), 3-chymotrypsin-like cysteine protease (3CLpro), and RNA-dependent RNA polymerase (RdRp) play significant role in early and late phase of SARS-CoV-2 replication and translation. This review paper is based on the rationale of inhibiting of various SARS-CoV-2 proteins and enzymes as novel therapeutic approaches for the management and treatment of patients with SARS-CoV-2 infection. We also discussed the structural and functional relationship of different proteins and enzymes to develop therapeutic approaches for novel coronavirus SARS-CoV-2.

Keywords: 3CLpro; ACE2; Cyclophilin; Epidemiology; Nucleocapsid protein; Pathogenesis; RNA-dependent RNA polymerase; SARS-CoV-2; Spike protein; eIF4A.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2 / antagonists & inhibitors
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / metabolism
  • COVID-19 / metabolism
  • COVID-19 Drug Treatment*
  • COVID-19 Vaccines / administration & dosage*
  • COVID-19 Vaccines / metabolism
  • Drug Delivery Systems / methods*
  • Drug Repositioning
  • Humans
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / metabolism
  • Virus Replication / drug effects
  • Virus Replication / physiology

Substances

  • Antiviral Agents
  • COVID-19 Vaccines
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2