英国布里斯托大学Christiane Schaffitzel、Imre Berger等研究人员合作发现SARS-CoV-2突刺蛋白中的游离脂肪酸结合口袋。相关论文于2020年9月21日在线发表于国际学术期刊《科学》。
Title: Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein
Author: Christine Toelzer, Kapil Gupta, Sathish K. N. Yadav, Ufuk Borucu, Andrew D. Davidson, Maia Kavanagh Williamson, Deborah K. Shoemark, Frederic Garzoni, Oskar Staufer, Rachel Milligan, Julien Capin, Adrian J. Mulholland, Joachim Spatz, Daniel Fitzgerald, Imre Berger, Christiane Schaffitzel
Issue&Volume: 2020/09/21
Abstract: COVID-19, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), represents a global crisis. Key to SARS-CoV-2 therapeutic development is unraveling the mechanisms driving high infectivity, broad tissue tropism and severe pathology. Our 2.85 cryo-EM structure of SARS-CoV-2 spike (S) glycoprotein reveals that the receptor binding domains (RBDs) tightly bind the essential free fatty acid (FFA) linoleic acid (LA) in three composite binding pockets. The pocket also appears to be present in the highly pathogenic coronaviruses SARS-CoV and MERS-CoV. LA binding stabilizes a locked S conformation giving rise to reduced ACE2 interaction in vitro. In human cells, LA supplementation synergizes with the COVID-19 drug remdesivir, suppressing SARS-CoV-2 replication. Our structure directly links LA and S, setting the stage for intervention strategies targeting LA binding by SARS-CoV-2.
DOI: 10.1126/science.abd3255
Source: https://science.sciencemag.org/content/early/2020/09/18/science.abd3255