RT Journal Article
SR Electronic
T1 Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.27.428428
DO 10.1101/2021.01.27.428428
A1 C. Joaquín Cáceres
A1 Stivalis Cardenas-Garcia
A1 Silvia Carnaccini
A1 Brittany Seibert
A1 Daniela S. Rajao
A1 Jun Wang
A1 Daniel R. Perez
YR 2021
UL http://biorxiv.org/content/early/2021/01/27/2021.01.27.428428.abstract
AB The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the defining global health emergency of this century. GC-376 is a Mpro inhibitor with antiviral activity against SARS-CoV-2 in vitro. Using the K18-hACE2 mouse model, the in vivo antiviral efficacy of GC-376 against SARS-CoV-2 was evaluated. GC-376 treatment was not toxic in K18-hACE2 mice and produced milder tissue lesions, reduced viral loads, fewer presence of viral antigen, and reduced inflammation in comparison to vehicle-treated controls, most notably in the brain in mice challenged with a low virus dose. Although GC-376 was not sufficient to improve neither clinical symptoms nor survival, it did show a positive effect against SARS-CoV-2 in vivo. This study supports the notion that the K18-hACE2 mouse model is suitable to study antiviral therapies against SARS-CoV-2, and GC-376 represents a promising lead candidate for further development to treat SARS-CoV-2 infection.Competing Interest StatementThe authors have declared no competing interest.