Famotidine as a drug alternative for SARS-CoV-2: A computer analysis.

Key Messages

By using computer modeling, this study sought to explain the antiviral effect of famotidine and determine if it is due to the drug’s ability to inhibit proteases (proteins) involved in the SARS-CoV-2 viral replication.

The results showed that famotidine could interact with the catalytic site of the three proteases associated with SARS-CoV-2 replication. However, the weak binding affinity of famotidine for these proteins suggests that a successful treatment with famotidine could likely be achieved only if it is combined with other antiviral drugs.

The analysis of famotidine's pharmacokinetic properties indicated that its effect against SARS-CoV2 infection will only be reached if given intravenously.

Biomolecules

Publication Date: June 24, 2020
Peer Reviewed: Yes
Publication Type: Original | Preclinical
DOI: https://www.doi.org/10.3390/biom10060954

Class A G Protein-Coupled Receptor Antagonist Famotidine as a Therapeutic Alternative Against SARS-CoV2: An In Silico Analysis

Joseph T. Ortega, Maria Luisa Serrano, Beata Jastrzebska

Abstract

The pandemic associated with Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV2) and its disease named COVID-19 challenged the scientific community to discover effective therapeutic solutions in a short period. Repurposing existing drugs is one viable approach that emphasizes speed during these urgent times. Famotidine, a class A G protein-coupled receptor antagonist used for the treatment of gastroesophageal reflux was recently identified in an in silico screening. Additionally, a recent retrospective clinical report showed that the treatment with famotidine provided a good outcome in patients infected with SARS-CoV2. A clinical trial testing effectiveness of famotidine in combination with hydroxychloroquine is currently ongoing in the United States (US). In the 1990s, famotidine was described as an antiviral agent against human immunodeficiency virus (HIV). Interestingly, some HIV protease inhibitors are presently being used against SARS-CoV2. However, it is not clear if famotidine could be effective against SARS-CoV2. Thus, by using a computational analysis, we aimed to examine if the antiviral effect of famotidine could be related to the inhibition of proteases involved in the virus replication. Our results showed that famotidine could interact within the catalytic site of the three proteases associated with SARS-CoV2 replication. However, weak binding affinity of famotidine to these proteases suggests that a successful famotidine therapy could likely be achieved only in combination with other antiviral drugs. Finally, analysis of famotidine’s pharmacokinetic parameters indicated that its effect against SARS-CoV2 infection could be reached only upon intravenous administration. This work will contribute to the pharmacological knowledge of famotidine as an antiviral agent against SARS-CoV2.