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.
Subject(s)
Antiviral Agents/administration & dosage , Benzylisoquinolines/administration & dosage , Betacoronavirus/drug effects , Calcium Channel Blockers/administration & dosage , Calcium Channels/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Animals , Antiviral Agents/adverse effects , Benzylisoquinolines/adverse effects , Betacoronavirus/pathogenicity , COVID-19 , Calcium Channel Blockers/adverse effects , Calcium Channels/metabolism , Coronavirus Infections/diagnosis , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Drug Interactions , Host-Pathogen Interactions , Humans , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , SARS-CoV-2 , Signal Transduction , COVID-19 Drug TreatmentSubject(s)
Antihypertensive Agents/administration & dosage , Coronavirus Infections/therapy , Hypertension/drug therapy , Pneumonia, Viral/therapy , Adrenergic beta-Antagonists/administration & dosage , Angiotensin Receptor Antagonists/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Antihypertensive Agents/adverse effects , COVID-19 , Calcium Channel Blockers/administration & dosage , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Diuretics/administration & dosage , Drug Administration Schedule , Germany , Hospitalization , Humans , Hypertension/diagnosis , Hypertension/mortality , Netherlands , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Protective Factors , Risk Factors , Treatment OutcomeABSTRACT
BACKGROUND: There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS: We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS: Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS: We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.