{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:01:56Z","timestamp":1791615716457,"version":"4.3.4"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,5,17]],"date-time":"2020-05-17T00:00:00Z","timestamp":1589673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100008897","name":"Janssen Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To characterize antiviral activity of the capsid assembly modulator (CAM-N) JNJ-56136379 against HBV genotypes and variants carrying amino acid substitutions in the core protein.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Anti-HBV activity of JNJ-56136379 was investigated against a diverse panel of 53 HBV clinical isolates (genotypes A\u2013H). The impact of core amino acid substitutions using site-directed mutants (SDMs) was assessed in a transient replication assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>JNJ-56136379 median 50% effective concentration (EC50) values across all genotypes were 10\u201333\u2009nM versus 17\u2009nM (genotype D reference). JNJ-56136379 remained active against isolates carrying nucleos(t)ide analogue resistance mutations (median EC50 2\u201325\u2009nM) or basal core promoter (BCP)\u2009\u00b1\u2009precore (PC) mutations (median EC50 13\u201320\u2009nM) or PC mutations (median EC50 11\u2009nM), representing activity against isolates from HBeAg-positive and -negative hepatitis B patients. Core amino acid substitutions in the CAM-binding pocket, when tested as SDMs at positions 23, 25, 30, 33, 37, 106, 110, 118, 124, 127 and 128, reduced JNJ-56136379 anti-HBV activity; EC50 fold increases ranged from 3.0 (S106T) to 85 (T33N). All substitutions were rare in a public database of &amp;gt;7600 HBV core sequences (frequencies 0.01%\u20130.3%). Nucleos(t)ide analogues retained full activity against these core SDMs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>JNJ-56136379, a potent HBV CAM-N, currently in Phase 2 clinical development, was generally fully active against an extensive panel of genotype A\u2013H clinical isolates, regardless of the presence of nucleos(t)ide analogue resistance or BCP\/PC mutations. JNJ-56136379 activity was reduced by some core amino acid substitutions in the CAM-binding pocket.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaa179","type":"journal-article","created":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T07:08:49Z","timestamp":1587971329000},"page":"2526-2534","source":"Crossref","is-referenced-by-count":30,"title":["Anti-HBV activity of the HBV capsid assembly modulator JNJ-56136379 across full-length genotype A\u2013H clinical isolates and core site-directed mutants in vitro"],"prefix":"10.1093","volume":"75","author":[{"given":"Thierry","family":"Verbinnen","sequence":"first","affiliation":[{"name":"Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Tan","sequence":"additional","affiliation":[{"name":"Janssen China Research & Development Center, 5F North Building #1 Jinchuang Mansion, 4560 Jinke Road, Shanghai 201210, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gengyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Janssen China Research & Development Center, 5F North Building #1 Jinchuang Mansion, 4560 Jinke Road, Shanghai 201210, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Dehertogh","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Vergauwen","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marc","family":"Neefs","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Jacoby","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Lenz","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Martin","family":"Berke","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,17]]},"reference":[{"key":"2020082404581213000_dkaa179-B1","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S2468-1253(18)30056-6","article-title":"Polaris Observatory Collaborators. 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