{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T21:44:39Z","timestamp":1758404679622,"version":"3.40.5"},"posted":{"date-parts":[[2020,9,24]]},"group-title":"In Review","reference-count":0,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2020,9,13]]},"abstract":"<title>Abstract<\/title>\n        <p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing COVID-19 pandemic. Successful development of vaccines and antivirals against SARS-CoV-2 requires a comprehensive understanding of the essential proteins of the virus. The envelope (E) protein of SARS-CoV-2 assembles into a cation-selective channel that mediates virus budding, release, and host inflammation response. E blockage reduces virus pathogenicity while E deletion attenuates the virus. Here we report the 2.4 \u00c5 structure and drug-binding site of E\u2019s transmembrane (TM) domain, determined using solid-state nuclear magnetic resonance (NMR) spectroscopy. In lipid bilayers that mimic the endoplasmic reticulum Golgi intermediate compartment (ERGIC) membrane, ETM forms a five-helix bundle surrounding a narrow central pore. The middle of the TM segment is distorted from the ideal a-helical geometry due to three regularly spaced phenylalanine residues, which stack within each helix and between neighboring helices. These aromatic interactions, together with interhelical Val and Leu interdigitation, cause a dehydrated pore compared to the viroporins of influenza and HIV viruses. Hexamethylene amiloride and amantadine bind shallowly to polar residues at the N-terminal lumen, while acidic pH affects the C-terminal conformation. These results indicate that SARS-CoV-2 E forms a structurally robust but bipartite channel whose N- and C-terminal halves can interact with drugs, ions and other viral and host proteins semi-independently. This structure establishes the atomic basis for designing E inhibitors as antiviral drugs against SARS-CoV-2.<\/p>","DOI":"10.21203\/rs.3.rs-77124\/v1","type":"posted-content","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T17:58:19Z","timestamp":1600970299000},"source":"Crossref","is-referenced-by-count":4,"title":["Structure and Drug Binding of the SARS-CoV-2 Envelope Protein in Phospholipid Bilayers"],"prefix":"10.21203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5255-5858","authenticated-orcid":false,"given":"Mei","family":"Hong","sequence":"first","affiliation":[{"name":"Massachusetts Institute of Technology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6358-0642","authenticated-orcid":false,"given":"Venkata","family":"Mandala","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"McKay","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5728-7175","authenticated-orcid":false,"given":"Alexander","family":"Shcherbakov","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aurelio","family":"Dregni","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonios","family":"Kolocouris","sequence":"additional","affiliation":[{"name":"National and Kapodidtrian University of Athens, Faculty of Pharmacy, Section of Pharmaceutical Chemistry"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/www.researchsquare.com\/article\/rs-77124\/v1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.researchsquare.com\/article\/rs-77124\/v1.html","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T23:34:36Z","timestamp":1659051276000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchsquare.com\/article\/rs-77124\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,24]]},"references-count":0,"URL":"https:\/\/doi.org\/10.21203\/rs.3.rs-77124\/v1","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1038\/s41594-020-00536-8","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2020,9,24]]},"subtype":"preprint"}}