Rapamycin as a potential repurpose drug candidate for the treatment of COVID-19

Chem Biol Interact. 2020 Nov 1:331:109282. doi: 10.1016/j.cbi.2020.109282. Epub 2020 Oct 6.

Abstract

The novel human coronavirus-2 (HCoV-2), called SARS-CoV-2, is the causative agent of Coronavirus Induced Disease (COVID-19) and has spread causing a global pandemic. Currently, there is no vaccine to prevent infection nor any approved drug for the treatment. The development of a new drug is time-consuming and cannot be relied on as a solution in combatting the immediate global challenge. In such a situation, the drug repurposing becomes an attractive solution to identify the potential of COVID-19 treatment by existing drugs, which are approved for other indications. Here, we review the potential use of rapamycin, an mTOR (Mammalian Target of Rapamycin) inhibitor that can be repurposed at low dosages for the treatment of COVID-19. Rapamycin inhibits protein synthesis, delays aging, reduces obesity in animal models, and inhibits activities or expression of pro-inflammatory cytokines such as IL-2, IL-6 and, IL-10. Overall, the use of rapamycin can help to control viral particle synthesis, cytokine storms and contributes to fight the disease by its anti-aging and anti-obesity effects. Since, rapamycin targets the host factors and not viral machinery, it represents a potent candidate for the treatment of COVID-19 than antiviral drugs as its efficacy is less likely to be dampened with high mutation rate of viral RNA. Additionally, the inhibitory effect of rapamycin on cell proliferation may aid in reducing viral replication. Therefore, by drug repurposing, low dosages of rapamycin can be tested for the potential treatment of COVID-19/SARS-CoV-2 infection.

Keywords: COVID-19; Drug repurposing; Rapamycin; SARS-CoV-2; mTOR.

Publication types

  • Review

MeSH terms

  • Betacoronavirus / isolation & purification
  • Betacoronavirus / physiology
  • COVID-19
  • Cell Proliferation / drug effects
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / pathology
  • Coronavirus Infections / virology
  • Cytokines / metabolism
  • Drug Repositioning*
  • Gene Expression / drug effects
  • Humans
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / pathology
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Sirolimus / pharmacology
  • Sirolimus / therapeutic use*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism
  • Virus Replication / drug effects

Substances

  • Cytokines
  • TOR Serine-Threonine Kinases
  • Sirolimus