Identification of potential COVID-19 treatment compounds which inhibit SARS Cov2 prototypic, Delta and Omicron variant infection

• Published in: Virology (New York, N.Y.) Vol. 572; pp. 64 - 71
• Main Authors: Kumar, Prabhakaran, Mathayan, Manikannan, Smieszek, Sandra P., Przychodzen, Bartlomiej P., Koprivica, Vuk, Birznieks, Gunther, Polymeropoulos, Mihael H., Prabhakar, Bellur S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2022; Academic Press
• Subjects: Anti-viral drug repurposing; Brief Communication; COVID-19 Drug Treatment; Delta; Humans; Omicron; SARS CoV2; SARS-CoV-2; Anti-viral drug repurposing; SARS CoV2; Omicron; Delta
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2022.05.004

Recurrent waves of COVID19 remain a major global health concern. Repurposing either FDA-approved or clinically advanced drug candidates can save time and effort required for validating the safety profile and FDA approval. However, the selection of appropriate screening approaches is key to identifying novel candidate drugs with a higher probability of clinical success. Here, we report a rapid, stratified two-step screening approach using pseudovirus entry inhibition assay followed by an infectious prototypic SARS CoV2 cytotoxic effect inhibition assay in multiple cell lines. Using this approach, we screened a library of FDA-approved and clinical-stage drugs and identified four compounds, apilimod, berbamine, cepharanthine and (S)-crizotinib which potently inhibited SARS CoV2-induced cell death. Importantly, these drugs exerted similar inhibitory effect on the delta and omicron variants although they replicated less efficiently than the prototypic strain. Apilimod is currently under clinical trial (NCT04446377) for COVID19 supporting the validity and robustness of our screening approach.
•A two-step antiviral screening of FDA-approved and clinical trial drugs against SARS CoV2 entry and cytotoxic effect.•Apilimod, Berbamine, Cepharanthine and (S)-Crizotinib potently inhibited prototypic SARS CoV2 entry and cytotoxic effect.•These compounds are effective against delta and omicron variants of concern in highly susceptible cell lines.