Repurposing calcium channel blockers as antiviral drugs
Vijayashree Priyadharsini Jayaseelancorresponding author and Arumugam Paramasivam
J Cell Commun Signal. 2020 Dec; 14(4): 467–468
The current pandemic caused by the SARS-CoV-2 has claimed over a half a million lives within a very short span of time. A therapeutic drug which could prevent the entry and propagation of the virus is the need of the hour. Several lines of evidence collected from experimental studies older than three decades have pointed out the fact that inhibiting calcium entry into cells can affect vital steps in the lifecycle of viruses. Hence, calcium channel blockers may be considered as an effective measure in the containment of the viruses. This commentary throws light two scientific papers although with divergent facts converging at a point by suggesting a promising treatment option for CoVID-19 (Fang et al. Lancet Respir Med 8:e21, 2020; Straus et al. J Virol 94:e00426, 2020).
FDA approved calcium channel blockers inhibit SARS-CoV-2 infectivity in epithelial lung cells
Marco R. Straus, Miya Bidon, Tiffany Tang, Gary R. Whittaker, Susan Daniel
doi: https://doi.org/10.1101/2020.07.21.214577. This article is a preprint and has not been certified by peer review [what does this mean?].
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.
COVID-19: Is it time to revisit the research on calcium channel drug targets?
DOI:10.33590/emjdiabet/200608Corpus ID: 219939920. Published 2020
As the COVID-19 outbreak continues to endanger global health and hamper the world economy, there are concerns and reconsiderations for medication taken by patients with cardiometabolic disorders as they are more vulnerable to COVID-19. While several articles and perspectives have dealt with the concern and safe continuation of antihypertensive drugs, there is paucity of information on calcium channel blockers (CCB). Despite the biology of calcium channel involvement in virus entry and replication, the beneficial effect of CCB is somewhat speculative and only preclinically evident. This commentary focusses on the clinical research on CCB in the context of COVID-19.