PropertyValue
?:abstract
  • COVID-19, caused by SARS-CoV-2, lacks effective therapeutics. Additionally, no antiviral drugs or vaccines were developed against the closely related coronavirus, SARS-CoV-1 or MERS-CoV, despite previous zoonotic outbreaks. To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through a combined mass spectrometry and X-ray approach against the SARS-CoV-2 main protease, one of two cysteine viral proteases essential for viral replication. Our crystallographic screen identified 71 hits that span the entire active site, as well as 3 hits at the dimer interface. These structures reveal routes to rapidly develop more potent inhibitors through merging of covalent and non-covalent fragment hits; one series of low-reactivity, tractable covalent fragments were progressed to discover improved binders. These combined hits offer unprecedented structural and reactivity information for on-going structure-based drug design against SARS-CoV-2 main protease.
is ?:annotates of
?:creator
?:journal
  • Nat_Commun
?:license
  • unk
?:publication_isRelatedTo_Disease
is ?:relation_isRelatedTo_publication of
?:source
  • WHO
?:title
  • Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease
?:type
?:who_covidence_id
  • #841208
?:year
  • 2020

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