Uncovering Flexible Active Site Conformations of SARS-CoV-2 3CL Proteases through Protease Pharmacophore Clusters and COVID-19 Drug Repurposing
Nikhil Pathak, Yun‐Ti Chen, Yen-Chao Hsu, Nung-Yu Hsu, Chih‐Jung Kuo, Hui Ping Tsai, Jaw‐Jou Kang, Chih-Heng Huang, Sui‐Yuan Chang, Yu-Hsiu Chang, Po‐Huang Liang, Jinn‐Moon Yang
Abstract
value of 3.28 μM. Analysis of binding mechanisms of protease inhibitors revealed the role of PPC core anchors. Our PPCs revealed the flexible protease active site conformations, which successfully enabled drug repurposing.
Topics & Concepts
BoceprevirProteaseTelaprevirPharmacophoreNelfinavirDrug repositioningActive siteChemistryProteasesProtease inhibitor (pharmacology)Virtual screeningAmprenavirVirologyComputational biologyBiologyDrugStereochemistryBiochemistryPharmacologyEnzymeViral loadHepatitis C virusVirusHIV-1 proteaseAntiretroviral therapyRibavirinComputational Drug Discovery MethodsSARS-CoV-2 and COVID-19 ResearchSynthesis and biological activity