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Here, we aim to (i) identify labile Zn-sites in viral proteins using guidelines established from our previous work and (ii) assess if clinically safe Zn-ejecting agents could eject Zn2+ from the predicted target site and thus inhibit viral replication. As proof-of-concept, we identified a labile Zn-site in the hepatitis C virus (HCV) NS5A protein and showed that the antialcoholism drug, disulfiram, could inhibit HCV replication to a similar extent as the clinically used antiviral agent, ribavirin. The discovery of a novel viral target and a new role for disulfiram in inhibiting HCV replication will enhance the therapeutic armamentarium against HCV. The strategy presented can also be applied to identify labile sites in other bacterial or viral proteins that can be targeted by disulfiram or other clinically safe Zn-ejectors.<\/jats:p>","DOI":"10.1021\/jacs.6b00299","type":"journal-article","created":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T12:00:38Z","timestamp":1456833638000},"page":"3856-3862","source":"Crossref","is-referenced-by-count":48,"title":["Using\nan Old Drug to Target a New Drug Site: Application\nof Disulfiram to Target the Zn-Site in HCV NS5A Protein"],"prefix":"10.1021","volume":"138","author":[{"given":"Yu-Ming","family":"Lee","sequence":"first","affiliation":[{"name":"Academia Sinica , , ,","place":["Taipei, Taiwan, 115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulander","family":"Duh","sequence":"additional","affiliation":[{"name":"Academia Sinica , , ,","place":["Taipei, Taiwan, 115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Academia Sinica , , ,","place":["Taipei, Taiwan, 115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.C.","family":"Lai","sequence":"additional","affiliation":[{"name":"Academia Sinica , , ,","place":["Taipei, Taiwan, 115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna S.","family":"Yuan","sequence":"additional","affiliation":[{"name":"Academia Sinica , , ,","place":["Taipei, Taiwan, 115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmay","family":"Lim","sequence":"additional","affiliation":[{"name":"Academia Sinica , , ,","place":["Taipei, Taiwan, 115"]},{"name":"National Tsing Hua University , , ,","place":["Hsinchu, Taiwan, 300"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2016,3,1]]},"reference":[{"key":"2026090114221240800_cit1","doi-asserted-by":"publisher","first-page":"6412","DOI":"10.1021\/ja00198a065","volume":"111","author":"Christianson","year":"1989","journal-title":"J. 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