{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:30:12Z","timestamp":1790371812582,"version":"4.1.0"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Currently approved oral antivirals for chronic HBV infection target the reverse transcriptase (RT) domain of the HBV polymerase. Emergence of drug resistance has been reported in a small proportion of chronic HBV patients on prolonged treatment with antivirals. We recently reported ZINC20451377, a small molecule targeting hepatitis B surface antigen (HBsAg) that effectively inhibits both WT HBV and tenofovir-resistant HBV. Due to the partial overlap between the RT domain and HBsAg, drug-resistant mutants are associated with corresponding mutations in HBsAg.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the efficacy of ZINC20451377 against nine clinically relevant drug-resistant HBV mutants that lead to simultaneous mutations in the overlapping HBsAg gene.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Huh7 cells were transfected with 1.2\u00d7 HBV replicons corresponding to WT HBV or drug-resistant HBV mutants and treated with different concentrations of ZINC20451377. We assessed the IC50 values of ZINC20451377 for HBsAg levels in the culture supernatants using ELISAs. HBV secretion was measured by immunocapture of secreted virions followed by real-time PCR quantitation of virion-associated DNA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>ZINC20451377 led to a dose-dependent inhibition of secreted HBsAg encoded by WT HBV and all nine drug-resistant mutants tested and the IC50 values were in the low micromolar range. ZINC20451377 inhibited HBV secretion from drug-resistant mutants except for mutants harbouring the rtL180M\u200a+\u200artM204V (MV) mutation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The small molecule ZINC20451377 inhibits HBsAg and virion secretion in some of the clinically relevant drug-resistant HBV mutants. ZINC20451377 has a modest overall effect, and it was not effective against the MV mutants (lamivudine- and entecavir-resistant mutants).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac148","type":"journal-article","created":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T19:09:42Z","timestamp":1650913782000},"page":"2120-2124","source":"Crossref","is-referenced-by-count":5,"title":["A small molecule targeting hepatitis B surface antigen inhibits clinically relevant drug-resistant hepatitis B virus"],"prefix":"10.1093","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9299-0387","authenticated-orcid":false,"given":"S","family":"Kiruthika","sequence":"first","affiliation":[{"name":"Kusuma School of Biological Sciences, Indian Institute of Technology Delhi , New Delhi , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchika","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Indian Institute of Technology Delhi , New Delhi , India"},{"name":"Supercomputing Facility for Bioinformatics & Computational Biology, Indian Institute of Technology Delhi , New Delhi , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5495-2213","authenticated-orcid":false,"given":"B","family":"Jayaram","sequence":"additional","affiliation":[{"name":"Kusuma School of Biological Sciences, Indian Institute of Technology Delhi , New Delhi , India"},{"name":"Department of Chemistry, Indian Institute of Technology Delhi , New Delhi , India"},{"name":"Supercomputing Facility for Bioinformatics & Computational Biology, Indian Institute of Technology Delhi , New Delhi , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4186-9939","authenticated-orcid":false,"given":"Perumal","family":"Vivekanandan","sequence":"additional","affiliation":[{"name":"Kusuma School of Biological Sciences, Indian Institute of 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