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It also becomes apparent from this structure how improvements in pharmacologic potency can be achieved by improving protein\u2013protein interaction stabilization and clear avenues for compound optimization are apparent from the data. The binding site observed in crystallography was biologically validated by mutational analysis, which also provides for the first time, to our knowledge, an understanding of a pathway by which viable, drug resistant virus variants may evolve against this drug class.<\/jats:p>","DOI":"10.1073\/pnas.1513803112","type":"journal-article","created":{"date-parts":[[2015,11,23]],"date-time":"2015-11-23T22:19:00Z","timestamp":1448317140000},"page":"15196-15201","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":158,"title":["High-resolution crystal structure of a hepatitis B virus replication inhibitor bound to the viral core protein"],"prefix":"10.1073","volume":"112","author":[{"given":"Klaus","family":"Klumpp","sequence":"first","affiliation":[{"name":"Novira Therapeutics, Doylestown, PA 18902;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M.","family":"Lam","sequence":"additional","affiliation":[{"name":"Novira Therapeutics, Doylestown, PA 18902;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Lukacs","sequence":"additional","affiliation":[{"name":"Beryllium, Bedford, MA 01730;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Vogel","sequence":"additional","affiliation":[{"name":"Novira Therapeutics, Doylestown, PA 18902;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suping","family":"Ren","sequence":"additional","affiliation":[{"name":"Novira Therapeutics, Doylestown, PA 18902;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Espiritu","sequence":"additional","affiliation":[{"name":"Novira Therapeutics, Doylestown, PA 18902;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Baydo","sequence":"additional","affiliation":[{"name":"Beryllium, Bedford, MA 01730;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kateri","family":"Atkins","sequence":"additional","affiliation":[{"name":"Beryllium, Bedford, MA 01730;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Abendroth","sequence":"additional","affiliation":[{"name":"Beryllium, Bedford, MA 01730;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guochun","family":"Liao","sequence":"additional","affiliation":[{"name":"Vista Informatics Corporation, San Mateo, CA 94403;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Efimov","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center, Philadelphia, PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Hartman","sequence":"additional","affiliation":[{"name":"Novira Therapeutics, Doylestown, PA 18902;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osvaldo A.","family":"Flores","sequence":"additional","affiliation":[{"name":"Novira Therapeutics, Doylestown, PA 18902;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2015,11,23]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"953","DOI":"10.3851\/IMP2654","article-title":"Mortality due to viral hepatitis in the Global Burden of Disease Study 2010: New evidence of an urgent global public health priority demanding action","volume":"18","author":"Cowie BC","year":"2013","unstructured":"BC Cowie, KS Carville, JH MacLachlan, Mortality due to viral hepatitis in the Global Burden of Disease Study 2010: New evidence of an urgent global public health priority demanding action. 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