Comparative study of a 3CL pro inhibitor and remdesivir against both major SARS-CoV-2 clades in human airway models.

BioRxiv : the Preprint Server for Biology
Maren de VriesMeike Dittmann

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of Coronavirus Disease 2019 (COVID-19), a pandemic that has claimed over 700,000 human lives. The only SARS-CoV-2 antiviral, for emergency use, is remdesivir, targeting the viral polymerase complex. PF-00835231 is a pre-clinical lead compound with an alternate target, the main SARS-CoV-2 protease 3CL pro (M pro ). Here, we perform a comparative analysis of PF-00835231 and remdesivir in A549 +ACE2 cells, using isolates of two major SARS-CoV-2 clades. PF-00835231 is antiviral for both clades, and, in this assay, statistically more potent than remdesivir. A time-of-drug-addition approach delineates the timing of early SARS-CoV-2 life cycle steps and validates PF-00835231's time of action. Both PF-00835231 and remdesivir potently inhibit SARS-CoV-2 in human polarized airway epithelial cultures. Thus, our study provides in vitro evidence for the potential of PF-00835231 as an effective antiviral for SARS-CoV-2, addresses concerns from non-human in vitro models, and supports further studies with this compound.

Citations

Jan 5, 2021·Frontiers in Pharmacology·Bruno Silva AndradeVasco Ariston de Carvalho Azevedo
Jan 14, 2021·The Biochemical Journal·George M Burslem
Feb 9, 2021·Saudi Journal of Biological Sciences·Pooi Ling MokSubbiah Suresh Kumar
Mar 27, 2021·Proceedings of the National Academy of Sciences of the United States of America·Xi HeDai Wang
Mar 16, 2021·Expert Opinion on Investigational Drugs·Binh T NgoIvan Fn Hung

Datasets Mentioned

BETA
GSE145926

Methods Mentioned

BETA
confocal microscopy
flow cytometry
scRNA-seq
bronchoalveolar lavages
sc-RNAseq
PCR
RNA-seq
chips
bronchoalveolar
lavages

Key Resources (RRID) Mentioned

SCR_016979

Related Concepts

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