Abstract
COVID-19 has infected more than 41 million people worldwide with over 1.1 million deaths and is caused by the severe acute respiratory syndrome coronavirus (CoV) 2 (SARS-CoV-2)(1). Currently there are no protective vaccinations available and the only antiviral therapy in active use in patients is remdesivir, which provides only limited benefit(2, 3). Hence, an urgent need for antiviral therapies against SARS-CoV-2 exists. SARS-CoV requires Ca2+ ions for host cell entry and based on the similarity between SARS-CoV and SARS-CoV-2 it is highly likely that the same requirements exist for both viruses(4, 5). Here, we tested whether FDA-approved calcium channel blocker (CCB) drugs can inhibit SARS-CoV-2 infection in cell culture. All the CCBs showed varying degrees of inhibition, with amlodipine and nifedipine strongly limiting SARS-CoV-2 entry and infection in epithelial lung cells at concentrations where cell toxicity was minimal. Further studies with pseudo-typed particles carrying the SARS CoV 2 Spike protein suggest that viral inhibition occurs at the level of viral host cell entry. Overall, our data suggest that CCBs have a high potential to treat SARS-CoV-2 infections and their current FDA approval would allow for a fast repurposing of these drugs.
Significance Covid-19 infections are still increasing around the globe and a number of countries are currently facing a second wave of infection resulting in re-instated lockdowns and dramatic consequences for the public health systems. Vaccine developments are in progress but as of now there are no efficacious drugs on the market to fight the pandemic. Here, we present the first case of a FDA-approved class of drugs that inhibit SARS CoV 2 growth in vitro. Their FDA approval may reduce the time for repurposing, allowing bypass of time-and cost-intensive animal models and to test them directly in clinical trials for human application for treatment of Covid-19.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Format changes in figures and text. Data added.