7nt4

X-ray structure of SCoV2-PLpro in complex with small molecule inhibitor

spinqualitylabelsall models 7nt4, resolution 2.68Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.68Å Ligands: EDO, PRL, SO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort and available vaccines, effective therapeutics are still missing to limit severe disease and mortality. Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PL(pro)) inhibitor. NMR titrations and a co-crystal structure confirm that acriflavine blocks the PL(pro) catalytic pocket in an unexpected binding mode. We show that the drug inhibits viral replication at nanomolar concentration in cellular models, in vivo in mice and ex vivo in human airway epithelia, with broad range activity against SARS-CoV-2 and other betacoronaviruses. Considering that acriflavine is an inexpensive drug approved in some countries, it may be immediately tested in clinical trials and play an important role during the current pandemic and future outbreaks. Acriflavine, a clinically approved drug, inhibits SARS-CoV-2 and other betacoronaviruses.,Napolitano V, Dabrowska A, Schorpp K, Mourao A, Barreto-Duran E, Benedyk M, Botwina P, Brandner S, Bostock M, Chykunova Y, Czarna A, Dubin G, Frohlich T, Holscher M, Jedrysik M, Matsuda A, Owczarek K, Pachota M, Plettenburg O, Potempa J, Rothenaigner I, Schlauderer F, Slysz K, Szczepanski A, Greve-Isdahl Mohn K, Blomberg B, Sattler M, Hadian K, Popowicz GM, Pyrc K Cell Chem Biol. 2022 Jan 11. pii: S2451-9456(21)00513-4. doi:, 10.1016/j.chembiol.2021.11.006. PMID:35021060 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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