000151173 001__ 151173
000151173 005__ 20251017144609.0
000151173 0247_ $$2doi$$a10.3390/biomedicines9040375
000151173 0248_ $$2sideral$$a125282
000151173 037__ $$aART-2021-125282
000151173 041__ $$aeng
000151173 100__ $$aRizzuti, Bruno
000151173 245__ $$aRutin Is a Low Micromolar Inhibitor of SARS-CoV-2 Main Protease 3CLpro: Implications for Drug Design of Quercetin Analogs
000151173 260__ $$c2021
000151173 5060_ $$aAccess copy available to the general public$$fUnrestricted
000151173 5203_ $$aThe pandemic, due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has stimulated the search for antivirals to tackle COVID-19 infection. Molecules with known pharmacokinetics and already approved for human use have been demonstrated or predicted to be suitable to be used either directly or as a base for a scaffold-based drug design. Among these substances, quercetin is known to be a potent in vitro inhibitor of 3CLpro, the SARS-CoV-2 main protease. However, its low in vivo bioavailability calls for modifications to its molecular structure. In this work, this issue is addressed by using rutin, a natural flavonoid that is the most common glycosylated conjugate of quercetin, as a model. Combining experimental (spectroscopy and calorimetry) and simulation techniques (docking and molecular dynamics simulations), we demonstrate that the sugar adduct does not hamper rutin binding to 3CLpro, and the conjugated compound preserves a high potency (inhibition constant in the low micromolar range, Ki = 11 \u03bcM). Although showing a disruption of the pseudo-symmetry in the chemical structure, a larger steric volume and molecular weight, and a higher solubility compared to quercetin, rutin is able to associate in the active site of 3CLpro, interacting with the catalytic dyad (His41Cys145). The overall results have implications in the drug-design of quercetin analogs, and possibly other antivirals, to target the catalytic site of the SARS-CoV-2 3CLpro.
000151173 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B25-20R$$9info:eu-repo/grantAgreement/ES/DGA/E45-20R$$9info:eu-repo/grantAgreement/ES/ISCIII/CPII13-00017$$9info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI18-00349-Investing in your future$$9info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/BES-2017-080739$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P
000151173 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000151173 590__ $$a4.757$$b2021
000151173 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b121 / 297 = 0.407$$c2021$$dQ2$$eT2
000151173 591__ $$aPHARMACOLOGY & PHARMACY$$b87 / 279 = 0.312$$c2021$$dQ2$$eT1
000151173 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b62 / 139 = 0.446$$c2021$$dQ2$$eT2
000151173 592__ $$a0.874$$b2021
000151173 593__ $$aMedicine (miscellaneous)$$c2021$$dQ1
000151173 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2021$$dQ1
000151173 594__ $$a3.0$$b2021
000151173 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000151173 700__ $$aGrande, Fedora
000151173 700__ $$aConforti, Filomena
000151173 700__ $$0(orcid)0000-0003-4726-7821$$aJimenez-Alesanco, Ana$$uUniversidad de Zaragoza
000151173 700__ $$aCeballos-Laita, Laura
000151173 700__ $$0(orcid)0000-0003-1885-4365$$aOrtega-Alarcon, David$$uUniversidad de Zaragoza
000151173 700__ $$0(orcid)0000-0002-1232-6310$$aVega, Sonia
000151173 700__ $$aReyburn, Hugh T.
000151173 700__ $$0(orcid)0000-0001-5664-1729$$aAbian, Olga$$uUniversidad de Zaragoza
000151173 700__ $$0(orcid)0000-0001-5702-4538$$aVelazquez-Campoy, Adrian$$uUniversidad de Zaragoza
000151173 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000151173 773__ $$g9, 4 (2021), 375 [20 pp.]$$tBiomedicines$$x2227-9059
000151173 8564_ $$s2730731$$uhttps://zaguan.unizar.es/record/151173/files/texto_completo.pdf$$yVersión publicada
000151173 8564_ $$s2761244$$uhttps://zaguan.unizar.es/record/151173/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000151173 909CO $$ooai:zaguan.unizar.es:151173$$particulos$$pdriver
000151173 951__ $$a2025-10-17-14:16:41
000151173 980__ $$aARTICLE