{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T01:08:35Z","timestamp":1773709715962,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,6]],"date-time":"2022-11-06T00:00:00Z","timestamp":1667692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tata Institute for Genetics and Society","award":["1R01EY032149-01"],"award-info":[{"award-number":["1R01EY032149-01"]}]},{"name":"Tata Institute for Genetics and Society","award":["1R01DK132735-01"],"award-info":[{"award-number":["1R01DK132735-01"]}]},{"name":"Tata Institute for Genetics and Society","award":["5R01AI163216-02"],"award-info":[{"award-number":["5R01AI163216-02"]}]},{"name":"National Institute of Health","award":["1R01EY032149-01"],"award-info":[{"award-number":["1R01EY032149-01"]}]},{"name":"National Institute of Health","award":["1R01DK132735-01"],"award-info":[{"award-number":["1R01DK132735-01"]}]},{"name":"National Institute of Health","award":["5R01AI163216-02"],"award-info":[{"award-number":["5R01AI163216-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>New variants of SARS-CoV-2 continue to evolve. The novel SARS-CoV-2 variant of concern (VOC) B.1.1.529 (Omicron) was particularly menacing due to the presence of numerous consequential mutations. In this study, we reviewed about 12 million SARS-CoV-2 genomic and associated metadata using extensive bioinformatic approaches to understand how evolutionary and mutational changes affect Omicron variant properties. Subsampled global data based analysis of molecular clock in the phylogenetic tree showed 29.56 substitutions per year as the evolutionary rate of five VOCs. We observed extensive mutational changes in the spike structural protein of the Omicron variant. A total of 20% of 7230 amino acid and structural changes exclusive to Omicron\u2019s spike protein were detected in the receptor binding domain (RBD), suggesting differential selection pressures exerted during evolution. Analyzing key drug targets revealed mutation-derived differential binding affinities between Delta and Omicron variants. Nine single-RBD substitutions were detected within the binding site of approved therapeutic monoclonal antibodies. T-cell epitope prediction revealed eight immunologically important functional hotspots in three conserved non-structural proteins. A universal vaccine based on these regions may likely protect against all these SARS-CoV-2 variants. We observed key structural changes in the spike protein, which decreased binding affinities, indicating that these changes may help the virus escape host cellular immunity. These findings emphasize the need for continuous genomic surveillance of SARS-CoV-2 to better understand how novel mutations may impact viral spread and disease outcome.<\/jats:p>","DOI":"10.3390\/v14112461","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T03:10:46Z","timestamp":1667790646000},"page":"2461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["In Silico Genome Analysis Reveals the Evolution and Potential Impact of SARS-CoV-2 Omicron Structural Changes on Host Immune Evasion and Antiviral Therapeutics"],"prefix":"10.3390","volume":"14","author":[{"given":"Dhruv","family":"Chauhan","sequence":"first","affiliation":[{"name":"Tata Institute for Genetics and Society, Centre at inStem, Bangalore 560065, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4603-1713","authenticated-orcid":false,"given":"Nikhil","family":"Chakravarty","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of California, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arjit Vijey","family":"Jeyachandran","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akshaya","family":"Jayakarunakaran","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjeev","family":"Sinha","sequence":"additional","affiliation":[{"name":"All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rakesh","family":"Mishra","sequence":"additional","affiliation":[{"name":"Tata Institute for Genetics and Society, Centre at inStem, Bangalore 560065, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vaithilingaraja","family":"Arumugaswami","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA"},{"name":"Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arunachalam","family":"Ramaiah","sequence":"additional","affiliation":[{"name":"Tata Institute for Genetics and Society, Centre at inStem, Bangalore 560065, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical Features of Patients Infected with 2019 Novel Coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ramaiah, A., and Arumugaswami, V. 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