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Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Biochem+Biophys+Res+Commun 2021 ; 555 (ä): 134-139 Nephropedia Template TP
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ALG-097111, a potent and selective SARS-CoV-2 3-chymotrypsin-like cysteine protease inhibitor exhibits in vivo efficacy in a Syrian Hamster model #MMPMID33813272
Biochem Biophys Res Commun 2021[May]; 555 (ä): 134-139 PMID33813272show ga
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 (IC(50) = 7 nM) without affecting the activity of human cathepsin L (IC(50) > 10 muM). 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) (TCID(50)/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.