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Filoviruses, including ebolaviruses and marburgviruses, can cause severe and often fatal disease in humans. Over the past several years, antibody therapy has emerged as a promising strategy for the treatment of filovirus disease. Here, we describe 2 distinct cross-reactive monoclonal antibodies (mAbs) isolated from mice immunized with recombinant vesicular stomatitis virus-based filovirus vaccines. Both mAbs recognized the glycoproteins of multiple different ebolaviruses and exhibited broad but differential in vitro neutralization activities against these viruses. By themselves, each mAb provided partial to full protection against Ebola virus in mice, and in combination, the mAbs provided 100% protection against Sudan virus challenge in guinea pigs. This study identified novel mAbs that were elicited through immunization and able to provide protection from ebolavirus infection, thus enriching the pool of candidate therapeutics for treating Ebola disease., Competing Interests: Potential conflicts of interest. A. W. has received royalties or licenses from Mapp Biopharmaceutical for a pan-ebolavirus antibody cocktail (MBP134); has patents planned, issued, or pending (US-11407817-B2, Monoclonal antibodies and cocktails for treatment of Ebola infections; US-11149080-B2, Methods of treating filovirus infections utilizing bispecific antibodies and fusion proteins that bind EBOV and NPC1; and US-10836810-B2, Monoclonal antibodies and cocktails for treatment of Ebola infections); and is an equity holder in Adimab LLC. K. C. has received grant funding from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) (grant number R01Al134824, paid to institution); has received royalties or licenses from Mapp Biopharmaceutical for a pan-ebolavirus antibody cocktail (MBP134) and from Q Squared Solutions for a COVID-19 spike neutralization assay; has received consulting fees from Axon Advisors, LLC; has patents planned, issued, or pending (US-11407817-B2, US-11149080-B2, and US-10836810-B2 [see above descriptions]); serves on the scientific advisory board for Integrum Scientific LLC; and is Chairman of the Board, equity holder, and stock or stock options holder for Eitr Biologics. L. B. has received grants or contracts from the NIH (project grant U19-AI142790-03) and the Canadian Safety and Security Program (project grant CSSP-2019-CP-2449). All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© His Majesty the King in Right of Canada, as represented by the Minister of Health (2023).)

Filoviruses such as Ebola virus (EBOV), Marburg virus (MARV), and Sudan virus (SUDV) cause deadly viral hemorrhagic fever in humans, with high case-fatality rates; however, no licensed therapeutic agent or vaccine has been clinically approved to treat or prevent infection. T-705 (favipiravir) is a novel antiviral drug that has been approved for the treatment of influenza in Japan. T-705 exhibits broad-spectrum antiviral activity against different viruses, including MARV and EBOV, and here, we are the first to report the in vitro and in vivo antiviral activity of T-705 against SUDV. T-705 treatment reduced SUDV replication in Vero E6 cells. Subcutaneous administration of T-705, beginning 1-4 days after infection and continuing for 7 days, significantly protected SUDV-infected guinea pigs, with a survival rate of 83%-100%. Viral RNA replication and infectious virus production were also significantly reduced in the blood, spleen, liver, lungs, and kidney. Moreover, early administration of low-dose T-705 and late administration (at 5 days after infection) of higher-dose T-705 also showed partial protection. Overall, our study is the first to demonstrate the antiviral activity of T-705 against SUDV, suggesting that T-705 may be a potential drug candidate for use during outbreaks.