{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T17:42:11Z","timestamp":1788716531059,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:00:00Z","timestamp":1712188800000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The HIV capsid (CA) protein is a promising target for anti\u2010AIDS treatment due to its critical involvement in viral replication. Herein, we utilized the well\u2010documented CA inhibitor <jats:bold>PF74<\/jats:bold> as our lead compound and designed a series of low\u2010molecular\u2010weight phenylalanine derivatives. Among them, compound <jats:bold>7t<\/jats:bold> exhibited remarkable antiviral activity with a high selection index (EC<jats:sub>50<\/jats:sub>\u2009=\u20090.040\u2009\u00b5M, SI\u2009=\u20092815), surpassing that of <jats:bold>PF74<\/jats:bold> (EC<jats:sub>50<\/jats:sub>\u2009=\u20090.50\u2009\u00b5M, SI\u2009=\u2009258). Furthermore, when evaluated against the HIV\u20102 strain, <jats:bold>7t<\/jats:bold> (EC<jats:sub>50<\/jats:sub>\u2009=\u20090.13\u2009\u00b5M) demonstrated approximately 14\u2010fold higher potency than that of <jats:bold>PF74<\/jats:bold> (EC<jats:sub>50<\/jats:sub>\u2009=\u20091.76\u2009\u00b5M). Insights obtained from surface plasmon resonance (SPR) revealed that <jats:bold>7t<\/jats:bold> exhibited stronger target affinity to the CA hexamer and monomer in comparison to <jats:bold>PF74<\/jats:bold>. The potential interactions between <jats:bold>7t<\/jats:bold> and the HIV\u20101 CA were further elucidated using molecular docking and molecular dynamics simulations, providing a plausible explanation for the enhanced target affinity with <jats:bold>7t<\/jats:bold> over <jats:bold>PF74<\/jats:bold>. Moreover, the metabolic stability assay demonstrated that <jats:bold>7t<\/jats:bold> (<jats:italic>T<\/jats:italic><jats:sub>1\/2<\/jats:sub>\u2009=\u200977.0\u2009min) significantly outperforms <jats:bold>PF74<\/jats:bold> (<jats:italic>T<\/jats:italic><jats:sub>1\/2<\/jats:sub>\u2009=\u20090.7\u2009min) in human liver microsome, exhibiting an improvement factor of 110\u2010fold. In conclusion, <jats:bold>7t<\/jats:bold> emerges as a promising drug candidate warranting further investigation.<\/jats:p>","DOI":"10.1002\/jmv.29594","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T06:51:06Z","timestamp":1712299866000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Discovery of low\u2010molecular\u2010weight phenylalanine derivatives as novel HIV capsid modulators with improved antiretroviral activity and metabolic stability"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6224-2513","authenticated-orcid":false,"given":"Xiangyi","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University Jinan Shandong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University Jinan Shandong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prem Prakash","family":"Sharma","sequence":"additional","affiliation":[{"name":"HeteroChem InnoTech Hansraj College Campus (University of Delhi) Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit","family":"Kumar","sequence":"additional","affiliation":[{"name":"HeteroChem InnoTech Hansraj College Campus (University of Delhi) Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brijesh","family":"Rathi","sequence":"additional","affiliation":[{"name":"H.G. 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