{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T01:05:22Z","timestamp":1785287122379,"version":"3.55.0"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,8,27]],"date-time":"2015-08-27T00:00:00Z","timestamp":1440633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:p>Chikungunya virus (<jats:styled-content style=\"fixed-case\">CHIKV<\/jats:styled-content>) is a mosquito\u2010borne alphavirus. Recent outbreaks of <jats:styled-content style=\"fixed-case\">CHIKV<\/jats:styled-content> infections have been reported in <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>sia, <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>frica, and <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>urope. The symptoms of <jats:styled-content style=\"fixed-case\">CHIKV<\/jats:styled-content> infection include fever, headache, nausea, vomiting, myalgia, rash, and chronic persistent arthralgia. To date, no vaccines or selective antiviral drugs against this important emerging virus have been reported. In this study, the design, synthesis, and antiviral activity screening of new topographical peptidomimetics revealed three potential prototype agents <jats:bold>3a<\/jats:bold>,<jats:bold> 4b,<\/jats:bold> and <jats:bold>5d<\/jats:bold> showing 93\u2013100% maximum inhibition of <jats:styled-content style=\"fixed-case\">CHIKV<\/jats:styled-content> replication in cell\u2010based assay having <jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content><jats:sub>90<\/jats:sub> of 8.76\u20139.57\u00a0<jats:italic>\u03bc<\/jats:italic>g\/mL. Intensive molecular modeling studies including covalent docking, lowest unoccupied molecular orbital energies, and the atomic condensed Fukui functions calculations strongly suggested the covalent binding of peptidomimetics <jats:bold>3a<\/jats:bold>,<jats:bold> 4b,<\/jats:bold> and <jats:bold>5d<\/jats:bold> to <jats:styled-content style=\"fixed-case\">CHIKV<\/jats:styled-content> ns<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>2 protease leading to permanent enzyme inactivation via <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>ichael adduct formation between <jats:italic>\u03b1<\/jats:italic>\/<jats:italic>\u03b2<\/jats:italic>\u2010unsaturated ketone functionality in our designed peptidomimetics and active site catalytic cysteine1013. Furthermore, small molecular weight peptidomimetics <jats:bold>3a<\/jats:bold> and <jats:bold>4b<\/jats:bold> satisfied the <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>ipinski rule of five for drug\u2010likeness and showed promising intestinal absorption and aqueous solubility via computational <jats:sc>admet<\/jats:sc> studies making them promising hits for further optimization.<\/jats:p>","DOI":"10.1111\/cbdd.12621","type":"journal-article","created":{"date-parts":[[2015,7,25]],"date-time":"2015-07-25T13:28:51Z","timestamp":1437830931000},"page":"1518-1527","source":"Crossref","is-referenced-by-count":24,"title":["Discovery of Novel Peptidomimetics as Irreversible <scp>CHIKV<\/scp> Ns<scp>P<\/scp>2 Protease Inhibitors Using Quantum Mechanical\u2010Based Ligand Descriptors"],"prefix":"10.1111","volume":"86","author":[{"given":"Eman M.","family":"El\u2010labbad","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy Ain Shams University Abbassia Cairo 11566 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed A. 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