{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:44:10Z","timestamp":1787165050515,"version":"build-2736575974"},"reference-count":15,"publisher":"Microbiology Society","issue":"1","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council","award":["MR\/S001026\/1"],"award-info":[{"award-number":["MR\/S001026\/1"]}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"crossref","award":["2016\/03807-0"],"award-info":[{"award-number":["2016\/03807-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"crossref","award":["2018\/04678-5"],"award-info":[{"award-number":["2018\/04678-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:p>Hepatitis C virus (HCV) genotype 3 presents a high level of both baseline and acquired resistance to direct-acting antivirals (DAAs), particularly those targeting the NS5A protein. To understand this resistance we studied a cohort of Brazilian patients treated with the NS5A DAA, daclatasvir and the nucleoside analogue, sofosbuvir. We observed a novel substitution at NS5A amino acid residue 98 [serine to glycine (S98G)] in patients who relapsed post-treatment. The effect of this substitution on both replication fitness and resistance to DAAs was evaluated using two genotype 3 subgenomic replicons. S98G had a modest effect on replication, but in combination with the previously characterized resistance-associated substitution (RAS), Y93H, resulted in a significant increase in daclatasvir resistance. This result suggests that combinations of substitutions may drive a high level of DAA resistance and provide some clues to the mechanism of action of the NS5A-targeting DAAs.<\/jats:p>","DOI":"10.1099\/jgv.0.001496","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T12:22:16Z","timestamp":1604406136000},"source":"Crossref","is-referenced-by-count":2,"title":["A novel substitution in NS5A enhances the resistance of hepatitis C virus genotype 3 to daclatasvir"],"prefix":"10.1099","volume":"102","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1118-8486","authenticated-orcid":false,"given":"Guilherme Rodrigues","family":"Fernandes Campos","sequence":"first","affiliation":[{"name":"S\u00e3o Paulo State University, Institute of Biosciences, Languages and Exact Sciences, S\u00e3o Jos\u00e9 do Rio Preto, S\u00e3o Paulo State 15054-000, 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