{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T16:45:27Z","timestamp":1776012327572,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,10,2]],"date-time":"2020-10-02T00:00:00Z","timestamp":1601596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Institute on Minority Health and Health Disparities of the National Institutes of Health","award":["2U54MD007597"],"award-info":[{"award-number":["2U54MD007597"]}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["IIS 1924092"],"award-info":[{"award-number":["IIS 1924092"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DBI 2000296"],"award-info":[{"award-number":["DBI 2000296"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Howard University startup funds","award":["U100193"],"award-info":[{"award-number":["U100193"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The spike (S) glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the binding to the permissive cells. The receptor-binding domain (RBD) of SARS-CoV-2 S protein directly interacts with the human angiotensin-converting enzyme 2 (ACE2) on the host cell membrane. In this study, we used computational saturation mutagenesis approaches, including structure-based energy calculations and sequence-based pathogenicity predictions, to quantify the systemic effects of missense mutations on SARS-CoV-2 S protein structure and function. A total of 18\u00a0354 mutations in S protein were analyzed, and we discovered that most of these mutations could destabilize the entire S protein and its RBD. Specifically, residues G431 and S514 in SARS-CoV-2 RBD are important for S protein stability. We analyzed 384 experimentally verified S missense variations and revealed that the dominant pandemic form, D614G, can stabilize the entire S protein. Moreover, many mutations in N-linked glycosylation sites can increase the stability of the S protein. In addition, we investigated 3705 mutations in SARS-CoV-2 RBD and 11\u00a0324 mutations in human ACE2 and found that SARS-CoV-2 neighbor residues G496 and F497 and ACE2 residues D355 and Y41 are critical for the RBD\u2013ACE2 interaction. The findings comprehensively provide potential target sites in the development of drugs and vaccines against COVID-19.<\/jats:p>","DOI":"10.1093\/bib\/bbaa233","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T15:12:32Z","timestamp":1598454752000},"page":"1239-1253","source":"Crossref","is-referenced-by-count":106,"title":["Systemic effects of missense mutations on SARS-CoV-2 spike glycoprotein stability and receptor-binding affinity"],"prefix":"10.1093","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8326-9889","authenticated-orcid":false,"given":"Shaolei","family":"Teng","sequence":"first","affiliation":[{"name":"Department of Biology at the Howard University, 415 College St. NW, Washington, DC 20059"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adebiyi","family":"Sobitan","sequence":"additional","affiliation":[{"name":"Department of Biology at the Howard University, 415 College St. NW, Washington, DC 20059"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raina","family":"Rhoades","sequence":"additional","affiliation":[{"name":"Department of Biology at the Howard University, 415 College St. NW, Washington, DC 20059"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongxiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Howard University College of Medicine, 520 W Street NW, Washington, DC 20059"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6487-2356","authenticated-orcid":false,"given":"Qiyi","family":"Tang","sequence":"additional","affiliation":[{"name":"Howard University College of Medicine, 520 W Street NW, Washington, DC 20059"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,10,2]]},"reference":[{"key":"2021042212443423200_ref1","doi-asserted-by":"crossref","DOI":"10.1186\/s12985-019-1182-0","article-title":"Coronavirus 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