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A cysteine protease inhibitor blocks SARS-CoV-2 infection of human and monkey cells

biorxiv. 2020; 
Drake Mellott, Chien-Te Tseng, Aleksandra Drelich, Pavla Fajtova, Bala C Chenna, Demetrios Kostomiris, Jason C Hsu, Jiyun Zhu, Zane Taylor, Vivian Tat, Ardala Katzfuss, Linfeng Li, Miriam A Giardini, Danielle Skinner, Ken Hirata, Sungjun Beck, Aaron F Carlin, Alex E Clark, Laura Berreta, Daniel Maneval, Felix Frueh, Brett L Hurst, Hong Wang, Klaudia I Kocurek, Frank M Raushel, Anthony O'Donoghue, Jair L Siqueira-Neto, Thomas D Meek, James H McKerrow
Products/Services Used Details Operation
Recombinant Antibody Expression … Biomedicals), and Z-LR-AMC (Enzo Life Sciences, Inc.). Recombinant SARS-CoV-1 spike protein was obtained from SinoBiological and SARS-CoV-2 spike was obtained from Genscript and Acro Biosystems. SARS-CoV-2 protease assays … Get A Quote

摘要

K777 is a di-peptide analog that contains an electrophilic vinyl-sulfone moiety and is a potent, covalent inactivator of cathepsins. Vero E6, HeLa/ACE2, Caco-2, A549/ACE2, and Calu-3, cells were exposed to SARS-CoV-2, and then treated with K777. K777 reduced viral infectivity with EC50 values of inhibition of viral infection of: 74 nM for Vero E6, <80 nM for A549/ACE2, and 4 nM for HeLa/ACE2 cells. In contrast, Calu-3 and Caco-2 cells had EC50 values in the low micromolar range. No toxicity of K777 was observed for any of the host cells at 10-100 μM inhibitor. K777 did not inhibit activity of the papain-like cysteine protease and 3CL cysteine protease, encoded by SARS-CoV-2 at concentrations of ≤ 100 μM. Th... More

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