{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T07:36:01Z","timestamp":1782372961342,"version":"3.54.5"},"reference-count":75,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural Research Program of the NIH","award":["75N91019D00024"],"award-info":[{"award-number":["75N91019D00024"]}]},{"name":"Intramural Research Program of the NIH","award":["1808705"],"award-info":[{"award-number":["1808705"]}]},{"DOI":"10.13039\/100000001","name":"NSF","doi-asserted-by":"publisher","award":["75N91019D00024"],"award-info":[{"award-number":["75N91019D00024"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"NSF","doi-asserted-by":"publisher","award":["1808705"],"award-info":[{"award-number":["1808705"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The global burden imposed by hepatitis B virus (HBV) infection necessitates the discovery and design of novel antiviral drugs to complement existing treatments. One attractive and underexploited therapeutic target is \u03b5, an ~85-nucleotide (nt) cis-acting regulatory stem-loop RNA located at the 3\u2032- and 5\u2032-ends of the pre-genomic RNA (pgRNA). Binding of the 5\u2032-end \u03b5 to the viral polymerase protein (P) triggers two early events in HBV replication: pgRNA and P packaging and reverse transcription. Our recent solution nuclear magnetic resonance spectroscopy structure of \u03b5 permits structure-informed drug discovery efforts that are currently lacking for P. Here, we employ a virtual screen against \u03b5 using a Food and Drug Administration (FDA)-approved compound library, followed by in vitro binding assays. This approach revealed that the anti-hepatitis C virus drug Daclatasvir is a selective \u03b5-targeting ligand. Additional molecular dynamics simulations demonstrated that Daclatasvir targets \u03b5 at its flexible 6-nt priming loop (PL) bulge and modulates its dynamics. Given the functional importance of the PL, our work supports the notion that targeting \u03b5 dynamics may be an effective anti-HBV therapeutic strategy.<\/jats:p>","DOI":"10.3390\/molecules28041803","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T01:38:18Z","timestamp":1676425098000},"page":"1803","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Virtual Screening of Hepatitis B Virus Pre-Genomic RNA as a Novel Therapeutic Target"],"prefix":"10.3390","volume":"28","author":[{"given":"Lukasz T.","family":"Olenginski","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech K.","family":"Kasprzak","sequence":"additional","affiliation":[{"name":"Bioinformatics and Computational Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon K.","family":"Attionu","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A.","family":"Shapiro","sequence":"additional","affiliation":[{"name":"RNA Biology Laboratory, National Cancer Institute, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore K.","family":"Dayie","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/S2468-1253(22)00124-8","article-title":"Global, regional, and national burden of hepatitis B, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"7","author":"Sheena","year":"2022","journal-title":"Lancet Gastroenterol. 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