Meike Dittmann - September 23, 2020

Meike Dittmann, PhD, Assistant Professor, Department of Microbiology, New York University Langone Health, "Comparative study of a 3CLpro inhibitor and remdesivir against both major SARS-CoV-2 clades in human airway models"

Nucleoside analogs such as remdesivir and inhibitors of viral proteases are important potential targets for therapeutics. There was a press release from Pfizer on initiation of Phase 1b clinical trial for a 3CL protease inhibitor, which was developed for SARS-CoV in 2003. It is intravenous treatment, so it is likely that it won’t be available outside the hospital setting. SARS-CoV-2 cytopathic effect on A549 cell overexpressing ACE2 (A549+ACE2) manifests as syncytia with nuclei arranged in ring-like structures. It was shown that the 3CL protease inhibitor has superior efficacy compared to that of remdesivir (A549+ACE2). Time-of-addition experiments revealed timing of polyprotein processing and the start of replication and transcription. It was demonstrated that polyprotein processing and replication follow each other closely in time. In addition, the antiviral efficacy was also tested with consistent results on polarized human airway epithelial cultures.