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Publication Abstract from PubMed

SARS-CoV-2 encodes three putative ion channels: E, 8a, and 3a. In related SARS-CoV-1, 3a is implicated in viral release, inflammasome activation, and cell death and its deletion reduces viral titer and morbidity in animal models, suggesting 3a-targeted therapeutics could treat SARS and COVID-19. However, the structural basis for the function of 3a is unknown. Here, we show that SARS-CoV-2 forms large conductance cation channels and present cryo-EM structures of dimeric and tetrameric SARS-CoV-2 3a in lipid nanodiscs. 3a adopts a novel fold and is captured in a closed or inactivated state. A narrow bifurcated exterior pore precludes conduction and leads to a large polar cavity open to the cytosol. 3a function is conserved in a common variant among circulating SARS-CoV-2 that alters the channel pore. We identify 3a-like proteins in Alpha- and Beta-coronaviruses that infect bats and humans, suggesting therapeutics targeting 3a could treat a range of coronaviral diseases.

Cryo-EM structure of the SARS-CoV-2 3a ion channel in lipid nanodiscs.,Kern DM, Sorum B, Hoel CM, Sridharan S, Remis JP, Toso DB, Brohawn SG bioRxiv. 2020 Jun 18. doi: 10.1101/2020.06.17.156554. PMID:32587976^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.