{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:13:58Z","timestamp":1790356438752,"version":"4.1.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,1,31]],"date-time":"2018-01-31T00:00:00Z","timestamp":1517356800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,1,31]],"date-time":"2018-01-31T00:00:00Z","timestamp":1517356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rift Valley fever virus (RVFV) is a mosquito-borne hemorrhagic fever virus affecting both humans and animals with severe morbidity and mortality and is classified as a potential bioterror agent due to the possible aerosol transmission. At present there is no human vaccine or antiviral therapy available. Thus, there is a great need to develop new antivirals for treatment of RVFV infections. Benzavir-2 was previously identified as potent inhibitor of human adenovirus, herpes simplex virus type 1, and type 2. Here we assess the anti-RVFV activity of benzavir-2 together with four structural analogs and determine pre-clinical pharmacokinetic parameters of benzavir-2. <jats:italic>In vitro<\/jats:italic>, benzavir-2 efficiently inhibited RVFV infection, viral RNA production and production of progeny viruses. <jats:italic>In vitro<\/jats:italic>, benzavir-2 displayed satisfactory solubility, good permeability and metabolic stability. In mice, benzavir-2 displayed oral bioavailability with adequate maximum serum concentration. Oral administration of benzavir-2 formulated in peanut butter pellets gave high systemic exposure without any observed toxicity in mice. To summarize, our data demonstrated potent anti-RVFV activity of benzavir-2 <jats:italic>in vitro<\/jats:italic> together with a promising pre-clinical pharmacokinetic profile. This data support further exploration of the antiviral activity of benzavir-2 in <jats:italic>in vivo<\/jats:italic> efficacy models that may lead to further drug development for human use.<\/jats:p>","DOI":"10.1038\/s41598-018-20362-9","type":"journal-article","created":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T11:11:59Z","timestamp":1516878719000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Anti-Rift Valley fever virus activity in vitro, pre-clinical pharmacokinetics and oral bioavailability of benzavir-2, a broad-acting antiviral compound"],"prefix":"10.1038","volume":"8","author":[{"given":"Md. Koushikul","family":"Islam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e5rten","family":"Strand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Saleeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Svensson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Baranczewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3708-7395","authenticated-orcid":false,"given":"Per","family":"Artursson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6ran","family":"Wadell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clas","family":"Ahlm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Elofsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Evander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,1,31]]},"reference":[{"key":"20362_CR1","doi-asserted-by":"publisher","first-page":"22","DOI":"10.4269\/ajtmh.2010.09-0318","volume":"83","author":"M Mohamed","year":"2010","unstructured":"Mohamed, M. et al. Epidemiologic and clinical aspects of a Rift Valley fever outbreak in humans in Tanzania, 2007. The American journal of tropical medicine and hygiene 83, 22\u201327, https:\/\/doi.org\/10.4269\/ajtmh.2010.09-0318 (2010).","journal-title":"The American journal of tropical medicine and hygiene"},{"key":"20362_CR2","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1086\/345671","volume":"36","author":"M Al-Hazmi","year":"2003","unstructured":"Al-Hazmi, M. et al. Epidemic Rift Valley fever in Saudi Arabia: a clinical study of severe illness in humans. Clin Infect Dis 36, 245\u2013252, https:\/\/doi.org\/10.1086\/345671 (2003).","journal-title":"Clin Infect Dis"},{"key":"20362_CR3","doi-asserted-by":"publisher","first-page":"ofw200","DOI":"10.1093\/ofid\/ofw200","volume":"3","author":"BM Boushab","year":"2016","unstructured":"Boushab, B. M. et al. Severe Human Illness Caused by Rift Valley Fever Virus in Mauritania, 2015. 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For all other authors there are no conflicts of interest to declare. None of the authors have any financial or funding disclosures to present.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"1925"}}