Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 555, Issue -, Pages 134-139Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.03.096
Keywords
COVID-19; Coronavirus; 3CLpro; Protease inhibitor
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There is an urgent need for antivirals targeting SARS-CoV-2 virus. SARS-CoV-2 main protease (3CLpro) is a promising target for antiviral therapy, but selectivity issues of inhibitors need to be addressed. ALG-097111 demonstrated potent inhibition of SARS-CoV-2 3CLpro in vivo, providing evidence for its potential as a therapeutic target.
There is an urgent need for antivirals targeting the SARS-CoV-2 virus to fight the current COVID-19 pandemic. The SARS-CoV-2 main protease (3CLpro) represents a promising target for antiviral therapy. The lack of selectivity for some of the reported 3CLpro inhibitors, specifically versus cathepsin L, raises potential safety and efficacy concerns. ALG-097111 potently inhibited SARS-CoV-2 3CLpro (IC50 = 7 mu M) without affecting the activity of human cathepsin L (IC50 > 10 mu M). When ALG-097111 was dosed in hamsters challenged with SARS-CoV-2, a robust and significant 3.5 log(10) (RNA copies/mg) reduction of the viral RNA copies and 3.7 log(10) (TCID50/mg) reduction in the infectious virus titers in the lungs was observed. These results provide the first in vivo validation for the SARS-CoV-2 3CLpro as a promising therapeutic target for selective small molecule inhibitors. (C) 2021 Elsevier Inc. All rights reserved.
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