{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T01:03:13Z","timestamp":1783040593423,"version":"3.54.6"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":52,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council for Medical Research","doi-asserted-by":"crossref","award":["VIR\/COVID-19\/19\/2021\/ECD-I"],"award-info":[{"award-number":["VIR\/COVID-19\/19\/2021\/ECD-I"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Veterans Affairs Merit Review","award":["BX005490"],"award-info":[{"award-number":["BX005490"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>As newer variants of SARS-CoV-2 continue to pose major threats to global human health and economy, identifying novel druggable antiviral targets is the key toward sustenance. Here, we identify an evolutionarily conserved \u201cEx3Lx6L\u201d (\u201cE-L-L\u201d) motif present within the HR2 domain of all human and nonhuman coronavirus spike (S) proteins that play a crucial role in stabilizing its postfusion six-helix bundle (6-HB) structure and thus, fusion-mediated viral entry. Mutations within this motif reduce the fusogenicity of the S protein without affecting its stability or membrane localization. We found that posaconazole, an FDA-approved drug, binds to this \u201cE-L-L\u201d motif and impedes the formation of 6-HB, thus effectively inhibiting SARS-CoV-2 infection in cells. While posaconazole exhibits high efficacy in blocking S protein-mediated viral entry, mutations within the \u201cE-L-L\u201d motif rendered the protein completely resistant to the drug, establishing its specificity toward this motif. Our data demonstrate that posaconazole restricts early stages of infection through specific inhibition of membrane fusion and viral genome release into the host cell and is equally effective toward all major variants of concerns of SARS-CoV-2, including Beta, Kappa, Delta, and Omicron. Together, we show that this conserved essential \u201cE-L-L\u201d motif is an ideal target for the development of prophylactic and therapeutic interventions against SARS-CoV-2.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgac198","type":"journal-article","created":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T08:42:28Z","timestamp":1666428148000},"source":"Crossref","is-referenced-by-count":19,"title":["Targeting an evolutionarily conserved \u201cE-L-L\u201d motif in spike protein to identify a small molecule fusion inhibitor against SARS-CoV-2"],"prefix":"10.1093","volume":"1","author":[{"given":"Indrani Das","family":"Jana","sequence":"first","affiliation":[{"name":"School of Bioscience, Indian Institute of Technology Kharagpur , Kharagpur 721302 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabuddha","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Mrinalini Datta Mahavidyapith , Kolkata 700051 , 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