Pharmacological hypothesis: TPC2 antagonist tetrandrine as a potential therapeutic agent for COVID-19
Paula M Heister1, Robin N Poston2
1University of Cambridge, Cambridge, United Kingdom.
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.
Insights
Tetrandrine, a compound from traditional Chinese medicine, may offer a new treatment for coronavirus disease 19 (COVID-19). Further research is needed to explore its potential as a therapeutic agent against SARS-CoV-2.
Area of Science:
- Pharmacology and Virology
- Drug Repurposing
- Traditional Chinese Medicine
Background:
- Coronavirus disease 19 (COVID-19), caused by SARS-CoV-2, has affected millions globally with no current vaccine or cure.
- Drug repurposing is a critical strategy for rapidly identifying potential therapeutics.
- Tetrandrine, a bisbenzylisoquinoline and calcium channel blocker from Stephania tetrandra, is used in traditional Chinese medicine.
Purpose of the Study:
- To hypothesize and review evidence for tetrandrine's potential as a COVID-19 treatment.
- To investigate tetrandrine's mechanism of action, particularly its antagonism of TPC2.
- To advocate for further research into tetrandrine's efficacy for COVID-19.
Main Methods:
- Literature review and evidence collation.
- Analysis of tetrandrine's known pharmacological properties.
- Examination of its interaction with two-pore channel 2 (TPC2).
Main Results:
- Tetrandrine exhibits antagonism of TPC2, a potential target in viral infections.
- Preliminary evidence suggests tetrandrine may be effective at clinically relevant doses.
- Limited existing pharmacological data necessitates further investigation.
Conclusions:
- Tetrandrine presents a promising candidate for COVID-19 therapeutic development.
- Its mechanism involving TPC2 warrants detailed study.
- Clinical research is recommended to validate tetrandrine's efficacy against SARS-CoV-2.
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