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As a result, we were able to identify 10 new Zika virus protease inhibitors. These compounds are natural products and showed strong inhibition in the biochemical assays. Inhibitory constants values for the compounds ranged from 5\u2005nM to 8\u2005\u03bcM. Among the most potent inhibitors are flavonoids like irigenol hexa\u2010acetate (K<jats:sub>i<\/jats:sub>=0.28\u2005\u03bcM), katacine (K<jats:sub>i<\/jats:sub>=0.26\u2005\u03bcM), theaflavin gallate (K<jats:sub>i<\/jats:sub>=0.40\u2005\u03bcM) and hematein (K<jats:sub>i<\/jats:sub>=0.33\u2005\u03bcM). Inhibitors from other groups of natural products include sennoside A (K<jats:sub>i<\/jats:sub>=0.19\u2005\u03bcM) and gossypol (K<jats:sub>i<\/jats:sub>=0.70\u2005\u03bcM). Several of the obtained compounds are known for their beneficial health effects and have acceptable pharmacokinetic characteristics. Thus, they could be of interest as lead compounds for the development of important and essential Zika antiviral drugs.<\/jats:p>","DOI":"10.1002\/cmdc.202100695","type":"journal-article","created":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T14:35:40Z","timestamp":1643726140000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Biochemical Screening of Potent Zika Virus Protease Inhibitors"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6904-8681","authenticated-orcid":false,"given":"Camila","family":"Coelho","sequence":"first","affiliation":[{"name":"Department of Science and Technology Federal University of S\u00e3o Paulo  330 Talim 12231-280 S\u00e3o Jos\u00e9 dos Campos Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6442-6604","authenticated-orcid":false,"given":"Gloria","family":"Gallo","sequence":"additional","affiliation":[{"name":"Department of Science and Technology Federal University of S\u00e3o Paulo  330 Talim 12231-280 S\u00e3o Jos\u00e9 dos Campos Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4177-6353","authenticated-orcid":false,"given":"Leon","family":"Hardy","sequence":"additional","affiliation":[{"name":"Department of Physics University of South Florida 4202 East Fowler Avenue  FL 33620-7100 Tampa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8429-0476","authenticated-orcid":false,"given":"Maria Elena","family":"Bottazzi","sequence":"additional","affiliation":[{"name":"Texas Children's Hospital Center for Vaccine Development Departments of Pediatrics and Molecular Virology &amp; 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