{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T15:03:08Z","timestamp":1789916588840,"version":"4.0.1"},"reference-count":49,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005363","name":"Universidad de Buenos Aires","doi-asserted-by":"publisher","award":["20020190100013BA"],"award-info":[{"award-number":["20020190100013BA"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 2021-1306"],"award-info":[{"award-number":["PICT 2021-1306"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas","doi-asserted-by":"publisher","award":["PIP11220170100171CO"],"award-info":[{"award-number":["PIP11220170100171CO"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases (Preclinical Services), National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN272201700041I"],"award-info":[{"award-number":["HHSN272201700041I"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The family Arenaviridae encompasses zoonotic, rodent-borne pathogens (e.g., Lassa, Machupo, and Jun\u00edn viruses) that cause severe viral hemorrhagic fevers with high case fatality rates. The current therapeutic landscape is severely limited, underscoring the urgent need for novel antiviral strategies. A promising approach involves combining directly acting antivirals with host-targeted antivirals. A compelling host-targeted antiviral target is the aryl hydrocarbon receptor (AHR). This ubiquitous ligand-activated transcription factor is a recognized pro-viral host factor across multiple viral families. Building on prior work with Jun\u00edn and Tacaribe viruses, we investigated whether the AHR inhibitor CH223191 could enhance the virus-directed antiviral activity of favipiravir against these viruses. First, we evaluated the toxicity and antiviral potential of CH223191 against a lethal Jun\u00edn virus infection in male and female hTfR1 mice. After demonstrating substantial protection, we conducted preliminary assays to study the antiviral effects of combining CH223191 and favipiravir on Tacaribe virus (TCRV) infections in the Vero cell culture model. We observed synergistic interaction with all four models (ZIP, Loewe, Bliss, and HSA). We next determined the sub-optimal dose of favipiravir and conducted an antiviral combination study in the AG129 mouse model infected with TCRV. The combination effectively protected mice from a lethal TCRV infection and showed cooperative effects, reducing weight loss and viral loads. Overall, these results show that the AHR is a promising pharmacological target for the development of novel antivirals. Furthermore, we discovered a cooperative interaction between the activities of favipiravir and CH223191.<\/jats:p>","DOI":"10.3390\/ijms27021071","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T13:59:54Z","timestamp":1769003994000},"page":"1071","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of the AHR Inhibitor CH223191 as an Adjunct Treatment for Mammarenavirus Infections"],"prefix":"10.3390","volume":"27","author":[{"given":"Miguel Angel","family":"Pelaez","sequence":"first","affiliation":[{"name":"Laboratorio de Estrategias Antivirales, Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Buenos Aires 1428, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3642-2980","authenticated-orcid":false,"given":"Jonna B.","family":"Westover","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dionna","family":"Scharton","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6431-7176","authenticated-orcid":false,"given":"Cybele Carina","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratorio de Estrategias Antivirales, Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Buenos Aires 1428, Argentina"},{"name":"Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), UBA-CONICET, Buenos Aires 1428, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9113-2575","authenticated-orcid":false,"given":"Brian B.","family":"Gowen","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1080\/21505594.2022.2054760","article-title":"Pathogenicity and Virulence of Marburg Virus","volume":"13","author":"Abir","year":"2022","journal-title":"Virulence"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Fl\u00f3rez-\u00c1lvarez, L., De Souza, E.E., Botosso, V.F., De Oliveira, D.B.L., Ho, P.L., Taborda, C.P., Palmisano, G., Capurro, M.L., Pinho, J.R.R., and Ferreira, H.L. 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