{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T09:20:11Z","timestamp":1771579211195,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human Pegivirus (HPgV) is an understudied flavivirus that is highly prevalent and often persists in the blood and tissues of humans. HPgV-infected brain tissue from individuals with Parkinson\u2019s disease has shown significant transcriptomic and immune signaling differences compared to non-infected Parkinson\u2019s brains. The HPgV genome is similar to Hepatitis C Virus (HCV), a well-characterized flavivirus with multiple approved small-molecule therapeutics. Here, we used HCV crystal structures to create homology models for two HPgV non-structural (NS) proteins, the serine protease (NS3) and the RNA-dependent RNA polymerase (NS5B), and performed molecular dynamic simulations. HCV and HPgV proteins had minimal structural differences, as seen by the Root Mean Square Deviation (RMSD) difference between NS3 (1.00 \u212b) and NS5B (1.26 \u212b). FDA-approved small molecules were then docked in silico to the NS3 and NS5B subunits of HCV and HPgV. HCV had weak to moderate correlated docking scores with HPgV NS3 (R2 = 0.21, p &lt; 0.001) and NS5B (R2 = 0.58, p &lt; 0.001). The predicted protein\u2013ligand interactions showed potential binding between HCV antivirals and conserved residues of HPgV, including the catalytic triad for NS3 or the GDD motif for NS5B. Together, these results provide structural insights for key HPgV proteins and highlight possibilities for therapeutic repurposing of HCV antivirals.<\/jats:p>","DOI":"10.3390\/v18020261","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T08:50:03Z","timestamp":1771577403000},"page":"261","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Silico Characterization of Two Human Pegivirus Proteins Highlights Similarities with Hepatitis C Virus and Possible Therapeutic Repurposing"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0906-7161","authenticated-orcid":false,"given":"Kaleigh M.","family":"Copenhaver","sequence":"first","affiliation":[{"name":"Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1060-9448","authenticated-orcid":false,"given":"Barbara A.","family":"Hanson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3740-9999","authenticated-orcid":false,"given":"Joshua J.","family":"Ziarek","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6836-1468","authenticated-orcid":false,"given":"Igor J.","family":"Koralnik","sequence":"additional","affiliation":[{"name":"Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"401","DOI":"10.4149\/av_2017_402","article-title":"The human pegivirus: A new name for an \u201cancient\u201d virus. can transfusion medicine come up with something new?","volume":"61","author":"Marano","year":"2017","journal-title":"Acta Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1080\/21505594.2022.2029328","article-title":"Review of human pegivirus: Prevalence, transmission, pathogenesis, and clinical implication","volume":"13","author":"Yu","year":"2022","journal-title":"Virulence"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.virol.2015.07.008","article-title":"Human pegivirus (HPgV; formerly known as GBV-C) inhibits IL-12 dependent natural killer cell function","volume":"485","author":"Chivero","year":"2015","journal-title":"Virology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1099\/vir.0.027490-0","article-title":"The GB viruses: A review and proposed classification of GBV-A, GBV-C (HGV), and GBV-D in genus pegivirus within the family Flaviviridae","volume":"92","author":"Stapleton","year":"2011","journal-title":"J. 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