000112027 001__ 112027
000112027 005__ 20230519145547.0
000112027 0247_ $$2doi$$a10.3390/ijms22137048
000112027 0248_ $$2sideral$$a127107
000112027 037__ $$aART-2021-127107
000112027 041__ $$aeng
000112027 100__ $$aMangiavacchi F.
000112027 245__ $$aSeleno-functionalization of quercetin improves the non-covalent inhibition of mpro and its antiviral activity in cells against sars-cov-2
000112027 260__ $$c2021
000112027 5060_ $$aAccess copy available to the general public$$fUnrestricted
000112027 5203_ $$aThe development of new antiviral drugs against SARS-CoV-2 is a valuable long-term strategy to protect the global population from the COVID-19 pandemic complementary to the vaccination. Considering this, the viral main protease (Mpro ) is among the most promising molecular targets in light of its importance during the viral replication cycle. The natural flavonoid quercetin 1 has been recently reported to be a potent Mpro inhibitor in vitro, and we explored the effect produced by the introduction of organoselenium functionalities in this scaffold. In particular, we report here a new synthetic method to prepare previously inaccessible C-8 seleno-quercetin derivatives. By screening a small library of flavonols and flavone derivatives, we observed that some compounds inhibit the protease activity in vitro. For the first time, we demonstrate that quercetin (1) and 8-(p-tolylselenyl)quercetin (2d) block SARS-CoV-2 replication in infected cells at non-toxic concentrations, with an IC50 of 192 µM and 8 µM, respectively. Based on docking experiments driven by experimental evidence, we propose a non-covalent mechanism for Mpro inhibition in which a hydrogen bond between the selenium atom and Gln189 residue in the catalytic pocket could explain the higher Mpro activity of 2d and, as a result, its better antiviral profile. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
000112027 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E45-17R$$9info:eu-repo/grantAgreement/ES/ISCIII/CPII13-00017$$9info:eu-repo/grantAgreement/ES/ISCIII-FIS/PI18-00349$$9info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/BES-2017-080739$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P
000112027 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000112027 590__ $$a6.208$$b2021
000112027 592__ $$a1.176$$b2021
000112027 594__ $$a6.9$$b2021
000112027 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b69 / 297 = 0.232$$c2021$$dQ1$$eT1
000112027 593__ $$aComputer Science Applications$$c2021$$dQ1
000112027 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b50 / 180 = 0.278$$c2021$$dQ2$$eT1
000112027 593__ $$aInorganic Chemistry$$c2021$$dQ1
000112027 593__ $$aSpectroscopy$$c2021$$dQ1
000112027 593__ $$aOrganic Chemistry$$c2021$$dQ1
000112027 593__ $$aPhysical and Theoretical Chemistry$$c2021$$dQ1
000112027 593__ $$aMolecular Biology$$c2021$$dQ1
000112027 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000112027 700__ $$aBotwina P.
000112027 700__ $$aMenichetti E.
000112027 700__ $$aBagnoli L.
000112027 700__ $$aRosati O.
000112027 700__ $$aMarini F.
000112027 700__ $$aFonseca S.F.
000112027 700__ $$aAbenante L.
000112027 700__ $$aAlves D.
000112027 700__ $$aDabrowska A.
000112027 700__ $$aKula-Pacurar A.
000112027 700__ $$0(orcid)0000-0003-1885-4365$$aOrtega-Alarcon D.$$uUniversidad de Zaragoza
000112027 700__ $$0(orcid)0000-0003-4726-7821$$aJimenez-Alesanco A.$$uUniversidad de Zaragoza
000112027 700__ $$0(orcid)0000-0003-1892-5063$$aCeballos-Laita L.
000112027 700__ $$0(orcid)0000-0002-1232-6310$$aVega S.
000112027 700__ $$aRizzuti B.
000112027 700__ $$0(orcid)0000-0001-5664-1729$$aAbian O.$$uUniversidad de Zaragoza
000112027 700__ $$aLenardão E.J.
000112027 700__ $$0(orcid)0000-0001-5702-4538$$aVelazquez-Campoy A.$$uUniversidad de Zaragoza
000112027 700__ $$aPyrc K.
000112027 700__ $$aSancineto L.
000112027 700__ $$aSanti C.
000112027 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000112027 773__ $$g22, 13 (2021), 22137048[20 pp]$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596
000112027 8564_ $$s2925097$$uhttps://zaguan.unizar.es/record/112027/files/texto_completo.pdf$$yVersión publicada
000112027 8564_ $$s2921021$$uhttps://zaguan.unizar.es/record/112027/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000112027 909CO $$ooai:zaguan.unizar.es:112027$$particulos$$pdriver
000112027 951__ $$a2023-05-18-15:46:28
000112027 980__ $$aARTICLE