000136106 001__ 136106
000136106 005__ 20240720100906.0
000136106 0247_ $$2doi$$a10.3390/ijms25116119
000136106 0248_ $$2sideral$$a139033
000136106 037__ $$aART-2024-139033
000136106 041__ $$aeng
000136106 100__ $$aPeralta-Moreno, M. N
000136106 245__ $$aShedding Light on Dark Chemical Matter: The Discovery of a SARS-CoV-2 Mpro Main Protease Inhibitor through Intensive Virtual Screening and In Vitro Evaluation
000136106 260__ $$c2024
000136106 5060_ $$aAccess copy available to the general public$$fUnrestricted
000136106 5203_ $$aThe development of specific antiviral therapies targeting SARS-CoV-2 remains fundamental because of the continued high incidence of COVID-19 and limited accessibility to antivirals in some countries. In this context, dark chemical matter (DCM), a set of drug-like compounds with outstanding selectivity profiles that have never shown bioactivity despite being extensively assayed, appears to be an excellent starting point for drug development. Accordingly, in this study, we performed a high-throughput screening to identify inhibitors of the SARS-CoV-2 main protease (Mpro) using DCM compounds as ligands. Multiple receptors and two different docking scoring functions were employed to identify the best molecular docking poses. The selected structures were subjected to extensive conventional and Gaussian accelerated molecular dynamics. From the results, four compounds with the best molecular behavior and binding energy were selected for experimental testing, one of which presented inhibitory activity with a Ki value of 48 ± 5 μM. Through virtual screening, we identified a significant starting point for drug development, shedding new light on DCM compounds
000136106 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P$$9info:eu-repo/grantAgreement/ES/MICINN/CEX2021-001202-M$$9info:eu-repo/grantAgreement/ES/MICINN/AEI/PID2021-127296OB-I00$$9info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/BES-2017-080739$$9info:eu-repo/grantAgreement/ES/ISCIII/PI21-00394$$9info:eu-repo/grantAgreement/ES/ISCIII-FIS/PI18-00349$$9info:eu-repo/grantAgreement/ES/DGA/E45-23R$$9info:eu-repo/grantAgreement/ES/DGA/B25-23R
000136106 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000136106 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000136106 700__ $$aMena, Y.
000136106 700__ $$0(orcid)0000-0003-1885-4365$$aOrtega-Alarcon, D.
000136106 700__ $$0(orcid)0000-0003-4726-7821$$aJiménez-Alesanco, A.$$uUniversidad de Zaragoza
000136106 700__ $$0(orcid)0000-0002-1232-6310$$aVega, S.
000136106 700__ $$0(orcid)0000-0001-5664-1729$$aAbian, O.$$uUniversidad de Zaragoza
000136106 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, A.$$uUniversidad de Zaragoza
000136106 700__ $$aThomson, T. M.
000136106 700__ $$aPinto, M.
000136106 700__ $$aGranadino-Roldán, J. M.
000136106 700__ $$aTomás, M.
000136106 700__ $$aPérez, J. J.
000136106 700__ $$aRubio-Martínez, J.
000136106 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000136106 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000136106 773__ $$g25, 11 (2024), 6119 [17 pp.]$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596
000136106 8564_ $$s2010873$$uhttps://zaguan.unizar.es/record/136106/files/texto_completo.pdf$$yVersión publicada
000136106 8564_ $$s2658816$$uhttps://zaguan.unizar.es/record/136106/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000136106 909CO $$ooai:zaguan.unizar.es:136106$$particulos$$pdriver
000136106 951__ $$a2024-07-19-18:54:29
000136106 980__ $$aARTICLE