{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T06:55:24Z","timestamp":1793084124380,"version":"4.5.0"},"posted":{"date-parts":[[2025,9,28]]},"group-title":"Bioinformatics","reference-count":83,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["U19AI171292"],"award-info":[{"award-number":["U19AI171292"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["R01GM140154"],"award-info":[{"award-number":["R01GM140154"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Filoviruses are enveloped, non-segmented, negative-strand RNA viruses belonging to the\n                  <jats:italic>Filoviridae<\/jats:italic>\n                  family, which includes five genera:\n                  <jats:italic>Ebolavirus<\/jats:italic>\n                  ,\n                  <jats:italic>Marburgvirus<\/jats:italic>\n                  ,\n                  <jats:italic>Cuevavirus, Striavirus<\/jats:italic>\n                  , and\n                  <jats:italic>Thamnovirus<\/jats:italic>\n                  . Members of this family cause severe and, often, fatal hemorrhagic fevers in humans and non-human primates, with high mortality rates. To date, only two filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), are known to infect humans and are listed as priority pathogens by the World Health Organization due to their potential for re-emergence and the current lack of effective vaccines and antiviral treatments. In this study, we identify and characterize conserved binding sites within key filoviral proteins to support the development of broad-spectrum, direct-acting antiviral agents. We validated the significance of these conserved regions for drug discovery using existing experimental data. Our analysis revealed notably high sequence similarity among proteins from filoviruses capable of infecting humans (EBOV, TAFV, BDBV, SUDV, MARV, and RAVV) compared to those from non-zoonotic species, with the highest conservation observed in the L and VP40 proteins\u2014both critical for viral genome transcription and replication. Furthermore, we compiled and analyzed available experimental data on known antiviral compounds targeting these proteins, identifying several agents with cross-filovirus activity, including Galidesivir, Remdesivir, and Favipiravir. The integrated approach described here\u2014combining sequence and structural conservation analysis with chemical structure and antiviral activity data\u2014demonstrates a strategy that could be extended to the development of broad-spectrum therapeutics across multiple viral families.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>HIGHLIGHTS<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Conserved filovirus sites targeted for broad-spectrum antivirals.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Structural modeling identifies key antiviral binding sites.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Viral internal proteins are crucial targets for inhibition.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Remdesivir validates conserved polymerase as a druggable target.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Study highlights need for pan-filovirus drug screening<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>TOC GRAPHIC<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"678902v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2025.09.26.678902","type":"posted-content","created":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T08:45:15Z","timestamp":1759049115000},"source":"Crossref","is-referenced-by-count":5,"title":["Conserved Filovirus Proteins as Targets of Broad-Spectrum Antivirals"],"prefix":"10.64898","author":[{"given":"Marcus Tullius","family":"Scotti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enes","family":"Kelestemur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holli-Joi","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Novy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleber C.","family":"Melo-Filho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata Priscila","family":"Barros de Menezes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chonny","family":"Herrera-Acevedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Tropsha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4616-7036","authenticated-orcid":false,"given":"Eugene N.","family":"Muratov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025093010001420000_2025.09.26.678902v1.1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.8.3743-3751.2006"},{"key":"2025093010001420000_2025.09.26.678902v1.2","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1093\/infdis\/jiy345","article-title":"In Vitro and In Vivo Activity of Amiodarone Against Ebola Virus","volume":"218","year":"2018","journal-title":"J. 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