Understanding Viral Infection Mechanisms and Patient Symptoms for the Development of COVID-19 Therapeutics

Int J Mol Sci. 2021 Feb 9;22(4):1737. doi: 10.3390/ijms22041737.

Abstract

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has become a worldwide pandemic. Symptoms range from mild fever to cough, fatigue, severe pneumonia, acute respiratory distress syndrome (ARDS), and organ failure, with a mortality rate of 2.2%. However, there are no licensed drugs or definitive treatment strategies for patients with severe COVID-19. Only antiviral or anti-inflammatory drugs are used as symptomatic treatments based on clinician experience. Basic medical researchers are also trying to develop COVID-19 therapeutics. However, there is limited systematic information about the pathogenesis of COVID-19 symptoms that cause tissue damage or death and the mechanisms by which the virus infects and replicates in cells. Here, we introduce recent knowledge of time course changes in viral titers, delayed virus clearance, and persistent systemic inflammation in patients with severe COVID-19. Based on the concept of drug reposition, we review which antiviral or anti-inflammatory drugs can effectively treat COVID-19 patients based on progressive symptoms and the mechanisms inhibiting virus infection and replication.

Keywords: ACE2; COVID-19; SARS-CoV-2; TMPRSS2; camostat mesilate; immunomodulation.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2 / metabolism
  • Antibodies, Monoclonal / therapeutic use
  • Antiviral Agents / therapeutic use
  • COVID-19 / complications
  • COVID-19 / pathology*
  • COVID-19 / virology
  • COVID-19 Drug Treatment
  • Cytokine Release Syndrome / etiology
  • Humans
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / physiology
  • Spike Glycoprotein, Coronavirus / metabolism
  • Viral Load
  • Virus Internalization

Substances

  • Antibodies, Monoclonal
  • Antiviral Agents
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2