3区 · 生物学
Article
作者: Chaltin, Patrick ; Bardiot, Dorothée ; Foo, Caroline S ; Neyts, Johan ; Jekle, Andreas ; Abdelnabi, Rana ; Chanda, Sushmita ; Jochmans, Dirk ; Vandyck, Koen ; Boland, Sandro ; Serebryany, Vladimir ; Blatt, Lawrence M ; Gupta, Kusum ; Raboisson, Pierre ; Symons, Julian A ; Marchand, Arnaud ; Dejonghe, Steven ; Vangeel, Laura ; Beigelman, Leonid ; Stoycheva, Antitsa ; Misner, Dinah ; Liu, Cheng ; Deval, Jerome ; Ren, Suping
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 nM) without affecting the activity of human cathepsin L (IC50 > 10 μM). When ALG-097111 was dosed in hamsters challenged with SARS-CoV-2, a robust and significant 3.5 log10 (RNA copies/mg) reduction of the viral RNA copies and 3.7 log10 (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.