{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jing L"],"funding":["Taishan Scholar Program of Shandong Province","Hercules Foundation (Research Foundation Flanders) and Rega Foundation, KU Leuven","National Natural Science Foundation of China","National Key Research and Development Program","Shandong Laboratory Program"],"pagination":["670"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11765572"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(2)"],"pubmed_abstract":["With the aim of developing novel anti-SARS-CoV-2 drugs to address the ongoing evolution and emergence of drug-resistant strains, the reported SARS-CoV-2 M<sup>pro</sup> inhibitor <b>WU-04</b> was selected as a lead to find novel, highly potent, and broad-spectrum inhibitors. Using a fragment-based multilevel virtual screening strategy, 15 hit compounds were identified and subsequently synthesized. Among them, <b>A5</b> (IC<sub>50</sub> = 1.05 μM), <b>A6</b> (IC<sub>50</sub> = 1.08 μM), and <b>A9</b> (IC<sub>50</sub> = 0.154 μM) demonstrated potent SARS-CoV-2 M<sup>pro</sup> inhibition comparable to or slightly weaker than <b>WU-04</b>. Antiviral activity evaluations revealed that compound <b>A9</b> exhibited the strongest antiviral activity with an EC<sub>50</sub> value of 0.18 μM, quite c"],"journal":["International journal of molecular sciences"],"pubmed_title":["Optimization of SARS-CoV-2 M&lt;sup&gt;pro&lt;/sup&gt; Inhibitors by a Structure-Based Multilevel Virtual Screening Method."],"pmcid":["PMC11765572"],"funding_grant_id":["the 'Caps-It' research infrastructure (project ZW13-02)","82373727","tsqn202408055","2023YFE0206500","SYS202205"],"pubmed_authors":["Zhan P","Liu X","Meng B","Neyts J","Jing L","Kang D","Zheng L","Zhao F","Jochmans D","Gao S","Laporte M","De Jonghe S"],"additional_accession":[]},"is_claimable":false,"name":"Optimization of SARS-CoV-2 M&lt;sup&gt;pro&lt;/sup&gt; Inhibitors by a Structure-Based Multilevel Virtual Screening Method.","description":"With the aim of developing novel anti-SARS-CoV-2 drugs to address the ongoing evolution and emergence of drug-resistant strains, the reported SARS-CoV-2 M<sup>pro</sup> inhibitor <b>WU-04</b> was selected as a lead to find novel, highly potent, and broad-spectrum inhibitors. Using a fragment-based multilevel virtual screening strategy, 15 hit compounds were identified and subsequently synthesized. Among them, <b>A5</b> (IC<sub>50</sub> = 1.05 μM), <b>A6</b> (IC<sub>50</sub> = 1.08 μM), and <b>A9</b> (IC<sub>50</sub> = 0.154 μM) demonstrated potent SARS-CoV-2 M<sup>pro</sup> inhibition comparable to or slightly weaker than <b>WU-04</b>. Antiviral activity evaluations revealed that compound <b>A9</b> exhibited the strongest antiviral activity with an EC<sub>50</sub> value of 0.18 μM, quite c","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jan","modification":"2026-05-27T08:02:44.765Z","creation":"2025-04-04T22:06:48.412Z"},"accession":"S-EPMC11765572","cross_references":{"pubmed":["39859382"],"doi":["10.3390/ijms26020670"]}}