20.500.12556/DKUM-78347 Ensemble Docking Coupled to Linear Interaction Energy Calculations for Identification of Coronavirus Main Protease (3CLpro) Non-Covalent Small-Molecule Inhibitors SARS-CoV-2, or severe acute respiratory syndrome coronavirus 2, represents a new strain of Coronaviridae. In the closing 2019 to early 2020 months, the virus caused a global pandemic of COVID-19 disease. We performed a virtual screening study in order to identify potential inhibitors of the SARS-CoV-2 main viral protease (3CLpro or Mpro). For this purpose, we developed a novel approach using ensemble docking high-throughput virtual screening directly coupled with subsequent Linear Interaction Energy (LIE) calculations to maximize the conformational space sampling and to assess the binding affinity of identified inhibitors. A large database of small commercial compounds was prepared, and top-scoring hits were identified with two compounds singled out, namely 1-[(R)-2-(1,3-benzimidazol-2-yl)-1-pyrrolidinyl]-2-(4-methyl-1,4-diazepan-1-yl)-1-ethanone and [({(S)-1-[(1H-indol-2-yl)methyl]-3-pyrrolidinyl}methyl)amino](5-methyl-2H-pyrazol-3-yl)formaldehyde. Moreover, we obtained a favorable binding free energy of the identified compounds, and using contact analysis we confirmed their stable binding modes in the 3CLpro active site. These compounds will facilitate further 3CLpro inhibitor design. COVID-19 SARS-CoV-2 Mpro 3CLpro 3C-like protease virtual screening inhibitors in silico drug design free-energy calculations izračunavanja inhibitorji pokazatelji proteaze koronavirusi true true true MDPI Angleški jezik Slovenski jezik Znanstveno delo 2020-12-10 23:28:53 2020-12-10 23:28:55 2025-01-25 03:11:15 2020-12-11 03:22:53 2020 0 0 Str. 1-11 št. 24, št. članka 5808 Letn. 25 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2020-11-05 2020-12-06 2020-12-09 578.834 42014467 10.3390/molecules25245808 1420-3049 URN:SI:UM:DK:MPK4OGWH Jukic-2020-Ensemble_Docking_Coupled_to_Linear.pdf Jukic-2020-Ensemble_Docking_Coupled_to_Linear.pdf 1 328FB87242D418E631F17D563AB2F367 152568b95adc84fda4c3fe63c450187b0443c761d64c7d6c90c9b44571cf90ba 6057ed9f-da29-11ef-9445-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=188105 https://doi.org/10.3390/molecules25245808 0 754fdf49-da29-11ef-9445-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=188106 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0