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Lead compounds for the development of SARS-CoV-2 3CL protease inhibitors

Sho Iketani, F. Forouhar, Hengrui Liu, Seo Jung Hong, Fang-Yu Lin, Manoj S. Nair, Arie Zask, Yaoxing Huang, Xing Li, Brent R. Stockwell, Alejandro Chavez, David D. Ho

2021Nature Communications114 citationsDOIOpen Access PDF

Abstract

We report the identification of three structurally diverse compounds - compound 4, GC376, and MAC-5576 - as inhibitors of the SARS-CoV-2 3CL protease. Structures of each of these compounds in complex with the protease revealed strategies for further development, as well as general principles for designing SARS-CoV-2 3CL protease inhibitors. These compounds may therefore serve as leads for the basis of building effective SARS-CoV-2 3CL protease inhibitors.

Topics & Concepts

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Coronavirus disease 2019 (COVID-19)2019-20 coronavirus outbreakProteaseVirologyCoronavirus InfectionsSars virusLead (geology)BetacoronavirusComputational biologyBiologyMedicineEnzymeBiochemistryOutbreakInfectious disease (medical specialty)DiseasePathologyPaleontologyComputational Drug Discovery MethodsSARS-CoV-2 and COVID-19 ResearchTuberculosis Research and Epidemiology
Lead compounds for the development of SARS-CoV-2 3CL protease inhibitors | Litcius