000147243 001__ 147243
000147243 005__ 20250923084442.0
000147243 0247_ $$2doi$$a10.1039/d4md00289j
000147243 0248_ $$2sideral$$a141059
000147243 037__ $$aART-2024-141059
000147243 041__ $$aeng
000147243 100__ $$aAguilera-Rodriguez, David
000147243 245__ $$aInhibition of SARS-CoV-2 3CLpro by chemically modified tyrosinase from <i>Agaricus bisporus</i>
000147243 260__ $$c2024
000147243 5060_ $$aAccess copy available to the general public$$fUnrestricted
000147243 5203_ $$aAntiviral compounds are crucial to controlling the SARS-CoV-2 pandemic. Approved drugs have been tested for their efficacy against COVID-19, and new pharmaceuticals are being developed as a complementary tool to vaccines. In this work, a cheap and fast purification method for natural tyrosinase from Agaricus bisporus (AbTyr) fresh mushrooms was developed to evaluate the potential of this enzyme as a therapeutic protein via the inhibition of SARS-CoV-2 3CLpro protease activity in vitro. AbTyr showed a mild inhibition of 3CLpro. Thus, different variants of this protein were synthesized through chemical modifications, covalently binding different tailor-made glycans and peptides to the amino terminal groups of the protein. These new tyrosinase conjugates were purified and characterized through circular dichroism and fluorescence spectroscopy analyses, and their stability was evaluated under different conditions. Subsequently, all these tyrosinase conjugates were tested for 3CLpro protease inhibition. From them, the conjugate between tyrosinase and a dextran-aspartic acid (6 kDa) polymer showed the highest inhibition, with an IC50 of 2.5 μg ml−1 and IC90 of 5 μg ml−1, with no cytotoxicity activity by polymer insertion. Finally, SARS-CoV-2 virus infection was studied. It was found that this new AbTyr-Dext6000 protein showed an 80% decrease in viral load. These results show the capacity of these tyrosinase bioconjugates as potential therapeutic proteins, opening the possibility of extension and applicability against other different viruses.
000147243 536__ $$9info:eu-repo/grantAgreement/ES/CSIC/PIE-202480E088$$9info:eu-repo/grantAgreement/ES/CSIC/PTI-Global Health SGL2103036
000147243 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000147243 590__ $$a3.6$$b2024
000147243 592__ $$a0.841$$b2024
000147243 591__ $$aCHEMISTRY, MEDICINAL$$b32 / 72 = 0.444$$c2024$$dQ2$$eT2
000147243 593__ $$aPharmaceutical Science$$c2024$$dQ1
000147243 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b129 / 319 = 0.404$$c2024$$dQ2$$eT2
000147243 593__ $$aOrganic Chemistry$$c2024$$dQ1
000147243 593__ $$aPharmacology$$c2024$$dQ2
000147243 593__ $$aDrug Discovery$$c2024$$dQ2
000147243 593__ $$aBiochemistry$$c2024$$dQ2
000147243 593__ $$aMolecular Medicine$$c2024$$dQ2
000147243 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000147243 700__ $$0(orcid)0000-0003-1885-4365$$aOrtega-Alarcon, David
000147243 700__ $$aVazquez-Calvo, Angela
000147243 700__ $$aRicci, Veronica
000147243 700__ $$0(orcid)0000-0001-5664-1729$$aAbian, Olga$$uUniversidad de Zaragoza
000147243 700__ $$0(orcid)0000-0001-5702-4538$$aVelazquez-Campoy, Adrian$$uUniversidad de Zaragoza
000147243 700__ $$aAlcami, Antonio
000147243 700__ $$aPalomo, Jose M.
000147243 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000147243 773__ $$g15, 12 (2024), 4159-4167$$pRSC med. chem.$$tRSC medicinal chemistry$$x2632-8682
000147243 8564_ $$s1826820$$uhttps://zaguan.unizar.es/record/147243/files/texto_completo.pdf$$yVersión publicada
000147243 8564_ $$s2857718$$uhttps://zaguan.unizar.es/record/147243/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000147243 909CO $$ooai:zaguan.unizar.es:147243$$particulos$$pdriver
000147243 951__ $$a2025-09-22-14:51:18
000147243 980__ $$aARTICLE