Pharmacological hypothesis: TPC2 antagonist tetrandrine as a potential therapeutic agent for COVID‐19
Tóm tắt
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.
Từ khóa
Tài liệu tham khảo
Shangbin Q, 1986, harmacology and Applications of Chinese Materia Medica (Volume I), 400
King VF, 1988, Interaction of tetrandrine with slowly inactivating calcium channels. Characterization of calcium channel modulation by an alkaloid of Chinese medicinal herb origin, J Biol Chem, 263, 2238, 10.1016/S0021-9258(18)69196-3
The Human Protein Atlas.2020https://www.proteinatlas.org/ENSG00000162341‐TPCN2/tissue
DobsonSJ MankouriJ WhitehouseA. A requirement for potassium and calcium channels during the endolysosomal trafficing of polyomavirus virions. bioR.xiv preprint 2019.
Dai GZ, 1990, Intravenous tetrandrine in terminating acute episodes of paroxysmal supraventricular tachycardia, Chin Med, 103, 460
BNF 79 March‐September 2020 RCPCH Publications Ltd 2020.
Guan S, 2001, Effect of tetrandrine on cellular electrophysiology and calcium uptake of myocardium in guinea pigs and dogs, Chin Med J, 114, 1046
Sun J, 2019, Clinical efficacy of acetylcysteine combined with tetrandrine tablets in the treatment of silicosis and the effect on serum IL‐6 and TNF‐alpha, Exp Ther Med, 18, 3383
Zhang J, 2020, Effects of tetrandrine combined with acetylcysteine on exercise tolerance, pulmonary function and serum TNF‐beta1 and MMP‐7 in silicosis patients, Exp Ther Med, 19, 2195
Seow WK, 1989, Suppression of human monocyte interleukin 1 production by the plant alkaloid tetrandrine, Clin Exp Immunol, 75, 47
Remy K, 2020, Immunotherapies for COVID‐19: lessons learned from sepsis, Lancet Respir Med, 1
Kannan S, 2014, Cochrane Database of Systematic Reviews
Xie QM, 2002, Pharmacological actions of tetrandrine in inflammatory pulmonary diseases, Acta Pharmacol Sin, 23, 1107
Dong Q‐K, 2011, Study on the pharmacokinetics of tetrandrine tablets in healthy volunteers, J Clin Med Pract, 15, 83
U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Guidance for Industry. Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers.2005.
Government UK, Medicines (Aristolochia and Mu Tong etc.) (Prohibition) Order 2001, SI 2001/1841
Cohen J, 2020, Mice, hamsters, ferrets, monkeys. Which lab animals can help defeat the new coronavirus?, Science