Alkyne Derivatives of SARS-CoV-2 Main Protease Inhibitors Including Nirmatrelvir Inhibit by Reacting Covalently with the Nucleophilic Cysteine

2023/02/09 by Lennart Brewitz, Leo Dumjahn, Yilin Zhao +13 · 1 voice · 5 citations
Chemistry · Medicine · Computer Science · #Click Chemistry and Applications #SARS-CoV-2 and COVID-19 Research #Computational Drug Discovery Methods

paper · doi:10.1021/acs.jmedchem.2c01627

openalex publication_date 2023/02/09 · openalex created_date 2023/02/10 · openalex updated_date 2026/07/23

Abstract

and other nucleophilic cysteine proteases by alkynes, which, in contrast to nitriles, can be functionalized at their terminal position to optimize inhibition and selectivity, as well as pharmacodynamic and pharmacokinetic properties.

Citations

• A new coronavirus associated with human respiratory disease in China
• The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2
• Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors
• Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors
• Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity

Cited by

• Mass spectrometric assays monitoring the deubiquitinase activity of the SARS-CoV-2 papain-like protease inform on the basis of substrate selectivity and have utility for substrate identification
• C6-Alkoxy substituted penicillins are potent non-covalently binding inhibitors of the SARS-CoV-2 main protease
• Silaproline-bearing nirmatrelvir derivatives are potent inhibitors of the SARS-CoV-2 main protease highlighting the value of silicon-derivatives in structure-activity-relationship studies
• Cephalosporins are potent SARS-CoV-2 main protease inhibitors
• Peptidyl nitroalkene inhibitors of main protease rationalized by computational and crystallographic investigations as antivirals against SARS-CoV-2

Discussions

• Have a look at the alkyne derivatives of SARS-CoV-2 main protease inhibitors here: doi.org/10.1021/acs.... 3/3 #GPS [bsky, 1 points, 0 comments]

Related

• C6-Alkoxy substituted penicillins are potent non-covalently binding inhibitors of the SARS-CoV-2 main protease
• Design, Synthesis, and Unprecedented Interactions of Covalent Dipeptide-Based Inhibitors of SARS-CoV-2 Main Protease and Its Variants Displaying Potent Antiviral Activity
• Cephalosporins are potent SARS-CoV-2 main protease inhibitors
• Silaproline-bearing nirmatrelvir derivatives are potent inhibitors of the SARS-CoV-2 main protease highlighting the value of silicon-derivatives in structure-activity-relationship studies
• Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors