articleJournal of the American Chemical SocietyFeb 10, 2022HYBRID OA

Ultralarge Virtual Screening Identifies SARS-CoV-2 Main Protease Inhibitors with Broad-Spectrum Activity against Coronaviruses

ALAndreas LuttensHGHjalmar GullbergEAEldar AbdurakhmanovDDDuy Duc VoDADario Akaberi

Uppsala University · Science for Life Laboratory · +7 more institutions

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Abstract

Drugs targeting SARS-CoV-2 could have saved millions of lives during the COVID-19 pandemic, and it is now crucial to develop inhibitors of coronavirus replication in preparation for future outbreaks. We explored two virtual screening strategies to find inhibitors of the SARS-CoV-2 main protease in ultralarge chemical libraries. First, structure-based docking was used to screen a diverse library of 235 million virtual compounds against the active site. One hundred top-ranked compounds were tested in binding and enzymatic assays. Second, a fragment discovered by crystallographic screening was optimized guided by docking of millions of elaborated molecules and experimental testing of 93 compounds. Three…

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Topics & keywords

Topics
Keywords
  • Chemistry
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
  • Coronavirus disease 2019 (COVID-19)
  • 2019-20 coronavirus outbreak
  • Broad spectrum
  • Virtual screening
  • Virology
  • Coronavirus
UN Sustainable Development Goals
  • Good health and well-being
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