{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T05:01:16Z","timestamp":1781154076843,"version":"3.54.1"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Syst. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolizing enzymes can significantly impact a patient\u2019s response to medication. Uridine diphosphate glucuronosyltransferase 1 family A1 and A4 (UGT1A1\/4) are crucial enzymes for metabolizing tecovirimat, the first oral antiviral drug approved for treating the monkeypox virus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study used a comprehensive in-silico workflow to assess the deleterious effects of 842 missense mutations and 308 SNPs in the non-coding regions of the UGT1A1 gene, alongside 700 missense mutations and 324 SNPs in the non-coding regions of the UGT1A4 gene. An ensemble of in-silico prediction, structural modelling, and docking tools was employed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified six missense variants that may compromise the structural integrity and function of the UGT1A1\/4 enzymes. Specifically, the UGT1A1 SNPs G308R, P356T and G374S, while in UGT1A4 the SNPs G309R, P357T and G375S, were predicted to be the most harmful missense SNPs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These mutations could affect drug-enzyme binding, potentially altering tecovirimat\u2019s therapeutic efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fsysb.2026.1821230","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T04:37:54Z","timestamp":1781152674000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational analysis and validation of UGT1A1\/4 missense variants impacting tecovirimat metabolism in monkeypox patients"],"prefix":"10.3389","volume":"6","author":[{"given":"Amro A.","family":"Abdelazim","sequence":"first","affiliation":[{"name":"International Dryland Development Commission (IDDC)","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameh E.","family":"Hassanein","sequence":"additional","affiliation":[{"name":"International Dryland Development Commission (IDDC)","place":["Cairo, Egypt"]},{"name":"Bioinformatics Program, School of Biotechnology, Nile University","place":["Giza, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Maged","sequence":"additional","affiliation":[{"name":"Applied Biotechnology Program, School of Biotechnology, Nile University","place":["Giza, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada S.","family":"Al-Theyab","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itoh","family":"Kimiko","sequence":"additional","affiliation":[{"name":"Institute of Science and Technology, Niigata University","place":["Niigata, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotb A.","family":"Attia","sequence":"additional","affiliation":[{"name":"Center of Excellence in Biotechnology Research, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2153","DOI":"10.1038\/s41598-025-85595-x","article-title":"In-silico screening and analysis of missense SNPs in human CYP3A4\/5 affecting drug-enzyme interactions of FDA-Approved COVID-19 antiviral drugs","volume":"15","author":"Abdelazim","year":"2025","journal-title":"Sci. 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