Abstract
ABSTRACTThe lack of coronavirus-specific antiviral drugs has instigated multiple drug repurposing studies to redirect previously approved medicines for the treatment of SARS-CoV-2, the coronavirus behind the ongoing COVID-19 pandemic. A recent, large-scale, retrospective clinical study showed that famotidine, when administered at a high dose to hospitalized COVID-19 patients, reduced the rates of intubation and mortality. A separate, patient-reported study associated famotidine use with improvements in mild to moderate symptoms such as cough and shortness of breath. While a prospective, multi-center clinical study is ongoing, two parallel in silico studies have proposed one of the two SARS-CoV-2 proteases, 3CLpro or PLpro, as potential molecular targets of famotidine activity; however, this remains to be experimentally validated. In this report, we systematically analyzed the effect of famotidine on viral proteases and virus replication. Leveraging a series of biophysical and enzymatic assays, we show that famotidine neither binds with nor inhibits the functions of 3CLpro and PLpro. Similarly, no direct antiviral activity of famotidine was observed at concentrations of up to 200 μM, when tested against SARS-CoV-2 in two different cell lines, including a human cell line originating from lungs, a primary target of COVID-19. These results rule out famotidine as a direct-acting inhibitor of SARS-CoV-2 replication and warrant further investigation of its molecular mechanism of action in the context of COVID-19.
Publisher
Cold Spring Harbor Laboratory
Reference41 articles.
1. Coronavirus puts drug repurposing on the fast track;Nat Biotechnol,2020
2. Beigel JH , Tomashek KM , Dodd LE , et al. Remdesivir for the Treatment of Covid-19 - Preliminary Report. N Engl J Med 2020.
3. Boulware DR , Pullen MF , Bangdiwala AS , et al. A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. N Engl J Med 2020.
4. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19;N Engl J Med,2020
5. Histamine H2-receptor antagonists;Nurs Clin North Am,1991
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