Pharmacological hypothesis: TPC2 antagonist tetrandrine as a potential therapeutic agent for COVID-19

Pharmacol Res Perspect. 2020 Oct;8(5):e00653. doi: 10.1002/prp2.653.

Abstract

More than ten million patients worldwide have been diagnosed with coronavirus disease 19 (COVID-19) to date (WHO situation report, 1st July 2020). There is no vaccine to prevent infection with the causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), nor a cure. In the struggle to devise potentially useful therapeutics in record time, the repurposing of existing compounds is a key route of action. In this hypothesis paper, we argue that the bisbenzylisoquinoline and calcium channel blocker tetrandrine, originally extracted from the plant Stephania tetrandra and utilized in traditional Chinese medicine, may have potential in the treatment of COVID-19 and should be further investigated. We collate and review evidence for tetrandrine's putative mechanism of action in viral infection, specifically its recently discovered antagonism of the two-pore channel 2 (TPC2). While tetrandrine's particular history of use provides a very limited pharmacological dataset, there is a suggestion from the available evidence that it could be effective at doses used in clinical practice. We suggest that further research to investigate this possibility should be conducted.

Keywords: SARS-CoV-2; calcium channel blocker; drug repurposing; endolysosomal pathway; traditional Chinese medicine; two-pore channel 2 (TPC2).

Publication types

  • Review

MeSH terms

  • Animals
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Benzylisoquinolines / administration & dosage*
  • Benzylisoquinolines / adverse effects
  • Betacoronavirus / drug effects*
  • Betacoronavirus / pathogenicity
  • COVID-19
  • COVID-19 Drug Treatment
  • Calcium Channel Blockers / administration & dosage*
  • Calcium Channel Blockers / adverse effects
  • Calcium Channels / drug effects*
  • Calcium Channels / metabolism
  • Coronavirus Infections / diagnosis
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / metabolism
  • Coronavirus Infections / virology
  • Drug Interactions
  • Host-Pathogen Interactions
  • Humans
  • Pandemics
  • Pneumonia, Viral / diagnosis
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / metabolism
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Signal Transduction

Substances

  • Antiviral Agents
  • Benzylisoquinolines
  • Calcium Channel Blockers
  • Calcium Channels
  • TPCN2 protein, human
  • tetrandrine