doi:10.3390/ph14090892engRizzuti, BrunoCeballos-Laita, LauraOrtega-Alarcon, DavidJimenez-Alesanco, AnaVega, SoniaGrande, FedoraConforti, FilomenaAbian, OlgaVelazquez-Campoy, AdrianSub-Micromolar Inhibition of SARS-CoV-2 3CLpro by Natural CompoundsART-2021-125275Inhibiting the main protease 3CLpro is the most common strategy in the search for antiviral drugs to fight the infection from SARS-CoV-2. We report that the natural compound eugenol is able to hamper in vitro the enzymatic activity of 3CLpro, the SARS-CoV-2 main protease, with an inhibition constant in the sub-micromolar range (Ki = 0.81 \u03bcM). Two phenylpropene analogs were also tested: the same effect was observed for estragole with a lower potency (Ki = 4.1 \u03bcM), whereas anethole was less active. The binding efficiency index of these compounds is remarkably favorable due also to their small molecular mass (MW < 165 Da). We envision that nanomolar inhibition of 3CLpro is widely accessible within the chemical space of simple natural compounds.2021http://zaguan.unizar.es/record/15116910.3390/ph14090892http://zaguan.unizar.es/record/151169oai:zaguan.unizar.es:151169info:eu-repo/grantAgreement/ES/DGA/B25-20Rinfo:eu-repo/grantAgreement/ES/DGA/E45-20Rinfo:eu-repo/grantAgreement/ES/ISCIII/CPII13-00017info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI18-00349-Investing in your futureinfo:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/BES-2017-080739info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/BFU2016-78232-PPharmaceuticals 14, 9 (2021), 892 [10 pp.]byhttps://creativecommons.org/licenses/by/4.0/deed.esinfo:eu-repo/semantics/openAccess