{"id":4228,"date":"2023-10-10T13:57:16","date_gmt":"2023-10-10T11:57:16","guid":{"rendered":"https:\/\/ospt.osi.lv\/2023\/10\/10\/macrocyclic-peptidomimetic-plasmepsin-x-inhibitors-with-potent-in-vitro-and-in-vivo-antimalarial-activity-2-2\/"},"modified":"2024-01-08T11:32:31","modified_gmt":"2024-01-08T09:32:31","slug":"pyrazolidinone-based-peptidomimetic-sars-cov-2-mpro-inhibitors","status":"publish","type":"post","link":"https:\/\/ospt.osi.lv\/pyrazolidinone-based-peptidomimetic-sars-cov-2-mpro-inhibitors\/","title":{"rendered":"48. Pyrazolidinone-based peptidomimetic SARS-CoV-2 Mpro inhibitors"},"content":{"rendered":"<div class=\"wpb-content-wrapper\"><p>[vc_row][vc_column][vc_column_text]Jelisejevs D., Bula A. L., Kinena L. <em><span dir=\"ltr\">Bioorg. Med. Chem. Lett. <\/span><\/em><strong><span dir=\"ltr\">2023<\/span><\/strong>, <em>96<\/em>, 129530<br \/>\nDOI: <a title=\"Pyrazolidinone-based peptidomimetic SARS-CoV-2 Mpro inhibitors\" href=\"https:\/\/doi.org\/10.1016\/j.bmcl.2023.129530\" target=\"_blank\" rel=\"nofollow noopener\">10.1016\/j.bmcl.2023.129530<\/a>.<\/p>\n<p>&nbsp;<\/p>\n<p><!--more--><\/p>\n<h4>Abstract<\/h4>\n<p style=\"text-align: justify;\">The main protease (M<sup>pro<\/sup>) of SARS-CoV-2 is an attractive drug target for COVID-19 treatment as it plays an integral role in the proliferation of coronavirus. Herein, we describe the investigation of <em>\u03b2<\/em>&#8211; and <em>\u03b3<\/em>-lactams as electrophilic \u201cwarheads\u201d for covalent binding to Cys145 of the M<sup>pro<\/sup> active site. The highest inhibitory activity (IC<sub>50<\/sub>\u00a0=\u00a045\u00a0\u00b1\u00a03\u00a0\u03bcM) was achieved using a pyrazolidinone warhead attached to the targeting dipeptide. Importantly, the synergy of the warhead and the targeting dipeptide is crucial for the successful inhibition of M<sup>pro<\/sup>.<\/p>\n<p>[\/vc_column_text][\/vc_column][\/vc_row]<\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>[vc_row][vc_column][vc_column_text]Jelisejevs D., Bula A. L., Kinena L. Bioorg. Med. Chem. Lett. 2023, 96, 129530 DOI: 10.1016\/j.bmcl.2023.129530. &nbsp;<\/p>\n","protected":false},"author":5,"featured_media":4262,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"image","meta":{"_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[16],"tags":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/posts\/4228"}],"collection":[{"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/users\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/comments?post=4228"}],"version-history":[{"count":6,"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/posts\/4228\/revisions"}],"predecessor-version":[{"id":4263,"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/posts\/4228\/revisions\/4263"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/media\/4262"}],"wp:attachment":[{"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/media?parent=4228"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/categories?post=4228"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ospt.osi.lv\/wp-json\/wp\/v2\/tags?post=4228"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}