{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T14:45:24Z","timestamp":1773499524391,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,6]],"date-time":"2021-03-06T00:00:00Z","timestamp":1614988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008783","name":"National Research Council of Science and Technology","doi-asserted-by":"publisher","award":["CRC-16-01-KRICT"],"award-info":[{"award-number":["CRC-16-01-KRICT"]}],"id":[{"id":"10.13039\/501100008783","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Zika virus (ZIKV), which is associated with severe diseases in humans, has spread rapidly and globally since its emergence. ZIKV and dengue virus (DENV) are closely related, and antibody-dependent enhancement (ADE) of infection between cocirculating ZIKV and DENV may exacerbate disease. Despite these serious threats, there are currently no approved antiviral drugs against ZIKV and DENV. The NS2B-NS3 viral protease is an attractive antiviral target because it plays a pivotal role in polyprotein cleavage, which is required for viral replication. Thus, we sought to identify novel inhibitors of the NS2B-NS3 protease. To that aim, we performed structure-based virtual screening using 467,000 structurally diverse chemical compounds. Then, a fluorescence-based protease inhibition assay was used to test whether the selected candidates inhibited ZIKV protease activity. Among the 123 candidate inhibitors selected from virtual screening, compound 1 significantly inhibited ZIKV NS2B-NS3 protease activity in vitro. In addition, compound 1 effectively inhibited ZIKV and DENV infection of human cells. Molecular docking analysis suggested that compound 1 binds to the NS2B-NS3 protease of ZIKV and DENV. Thus, compound 1 could be used as a new therapeutic option for the development of more potent antiviral drugs against both ZIKV and DENV, reducing the risks of ADE.<\/jats:p>","DOI":"10.3390\/microorganisms9030545","type":"journal-article","created":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T21:52:15Z","timestamp":1615153935000},"page":"545","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Structure-Based Virtual Screening: Identification of a Novel NS2B-NS3 Protease Inhibitor with Potent Antiviral Activity against Zika and Dengue Viruses"],"prefix":"10.3390","volume":"9","author":[{"given":"Hye Jin","family":"Shin","sequence":"first","affiliation":[{"name":"Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi-Hwa","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea"},{"name":"Bioenvironmental Science and Toxicology Division, Gyeongnam Branch Institute, Korea Institute of Toxicology, Jinju 52834, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joo-Youn","family":"Lee","sequence":"additional","affiliation":[{"name":"Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8038-1082","authenticated-orcid":false,"given":"Insu","family":"Hwang","sequence":"additional","affiliation":[{"name":"Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gun Young","family":"Yoon","sequence":"additional","affiliation":[{"name":"Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hae Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Chan","family":"Kwon","sequence":"additional","affiliation":[{"name":"Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8251-8820","authenticated-orcid":false,"given":"Dae-Gyun","family":"Ahn","sequence":"additional","affiliation":[{"name":"Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyun-Do","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bum-Tae","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8504-2872","authenticated-orcid":false,"given":"Seong-Jun","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chonsaeng","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4864","DOI":"10.1128\/JVI.00252-16","article-title":"Zika Virus: New Clinical Syndromes and Its Emergence in the Western Hemisphere","volume":"90","author":"Lazear","year":"2016","journal-title":"J. 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