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Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS., Methods: A list of therapies with anti-EBV effects was developed from existing reviews. A detailed review of pre-clinical and clinical data was undertaken to assess these candidates for potential usefulness and possible harm in MS. A 'drug-CV' and a plain language version focusing on tolerability aspects was created for each candidate. We used validated criteria to score each candidate with an international scientific panel and people living with MS., Results: A preliminary list of 11 drug candidates was generated. Following review by the scientific and lived experience expert panels, six yielded the same highest score. A further review by the expert panel shortlisted four drugs (famciclovir, tenofovir alafenamide, maribavir and spironolactone) deemed to have the best balance of efficacy, safety and tolerability for use in MS., Conclusions: Scientific and lived experience expert panel review of anti-EBV therapies selected four candidates with evidence for efficacy against EBV and acceptable safety and tolerability for potential use in phase III clinical trials for MS., Competing Interests: Declarations. Conflicts of Interest: V.L., F.McK., D.T., C.S., R.K., J.L.-S., A.L., B.T., J.M., L.S., G.G., S.S. and T.H. are recipients of or members of partner organisations on research grants for clinical trials of antiviral treatments for EBV in MS from the Australian Government Medical Research Future Fund (MRFF, 2023). D.T. has received research funding from the MRFF, Australian Research Council, the Australian National University and the Defence Materials Technology Centre. C.S. reports research and consultancy funding from Atara Biotherapeutics and has acted as a consultant for ATA188 program developing EBV immunotherapy for multiple sclerosis. He is a recipient of grants from MRFF and holds international patents or patent applications that cover CMV epitope sequences and their use in adoptive immunotherapy. R.K. is on the scientific advisory board of and is a consultant of Atara Biotherapeutics; is the editor-in-chief of Clinical and Translational Immunology; has patents or patents pending for T cell epitopes and immunotherapy for virus-associated diseases including malignancies and autoimmune diseases; received research support from Atara Biotherapeutics and National Health and Medical Research Council (NHMRC); and holds stock options in and received licensing payments from Atara Biotherapeutics. J.L.-S. has accepted travel compensation from Novartis, Biogen and Merck Healthcare KGaA (Darmstadt, Germany). Her institution receives the honoraria for talks and advisory board commitment as well as research grants from Janssen, Bayer Health Care, Biogen Idec, CSL, Celgene (BMS), Sanofi Genzyme, Merck, Roche, TEVA and Novartis. W.R. reports no disclosures relevant to the manuscript. A.L. has received investigator- initiated research grants from Gilead, Abbvie, Merck and Bristol-Myers Squibb. He has received investigator-initiated research grants from AbbVie, Gilead Sciences and Sequiris. He is supported by a Fellowship from NHMRC. B.T. or his institute have received honoraria for speaking from Merck and Novartis. He has served on advisory boards for Merck and Novartis and serves on the Australian National Blood Authority Scientific Working Group. L.S. has issued patents and an ongoing application for DNA vaccines for tolerance to myelin antigens, including GlialCAM (Pasithea Therapeutics) and has patent filings regarding antivirals for the treatment of MS. He is the principal investigator at Stanford University in the ATA188 trial with cell-based therapy for progressive MS. He has acted as a consultant for TG Therapeutics, 180 Life Sciences, BioAtla, Pasithea and Atreca; and is on Advisory or Data Safety Monitoring Boards for TG Therapeutics, Novartis, Receptos, Atreca, Tolerion, Teva and AbbVie; received travel funding and/or speaker honoraria from Celgene and AbbVie; received research support from Atara Biotherapeutics, Celgene and Biogen; holds stock options and board membership in Tolerion; and is a member of the board of directors of BioAtla. G.G. has received consulting or speaker fees from AbbVie, Aslan, Atara Bio, Biogen, Bristol Myers Squibb–Celgene, GlaxoSmithKline, GW Pharma, Janssen–Actelion, Japanese Tobacco, Jazz Pharmaceuticals, LifNano, Merck and Co, Merck KGaA–EMD Serono, Moderna, Novartis, Sanofi Genzyme, Roche-Genentech and Teva Pharmaceuticals. A.B.-O. has participated as a speaker in meetings sponsored by and received consulting fees and/or grant support from: Janssen/Actelion; Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Roche/Genentech, Medimmune, Merck/EMD Serono, Novartis and Sanofi-Genzyme. He has served on the scientific advisory boards of Receptos-Celgene, Sanofi/Genzyme, Roche/Genentech, Novartis, GSK, Atara Therapeutics, Guthy-Jackson Greater Good Foundation and Immune Tolerance Network. M.L. has received consulting fees from Alexion, Viela Bio, Genentech/Roche/Chugai, Quest Diagnostics and UCB Pharmaceuticals. N.D., A.P., N.C., L.S., E.B. and B.F. report no disclosures relevant to the manuscript. S.H. serves on advisory boards for Merck Healthcare KGaA (Darmstadt, Germany), Biogen, Novartis, Sanofi, Roche and Bayer. She has received money for travel and speaker honorarium from Biogen, Sanofi, Novartis, Merck Healthcare KGaA (Darmstadt, Germany), Roche and Bayer. T.H. has received speaking fees or received honoraria for serving on advisory boards for Bayer, Biogen, Merck, Teva, Novartis, Roche, Bristol Myers Squibb and Sanofi-Genzyme. S.B. has received honoraria for attendance at advisory boards and travel sponsorship from Bayer-Schering, Biogen-Idec, Merck-Serono, Novartis, and Sanofi-Genzyme, TEVA and CSL; has received speakers’ honoraria from Biogen-Idec and Genzyme; is an investigator in clinical trials sponsored by Biogen Idec, Novartis and Genzyme and ATARA; and was the recipient of an unencumbered research grant from Biogen-Idec. Availability of data and material: Data supporting the findings of this study are provided in the Online Resource file. Funding: No funding was received to assist with the preparation of this manuscript. Ethics: The study was approved by the Griffith University Human Research Ethics Committee, GU2024/155 and conducted in accordance with principles of the 1964 Declaration of Helsinki and its later amendments. Consent to participate: Not applicable. Consent for publication: Not applicable. Code availability: Not Applicable. Author contributions: S.B. conceived the idea; S.B., S.H. and G.G. proposed drug candidates for consideration from existing reviews; V.L. and F.McK. prepared scientific and plain language drug summaries; V.L., wrote the first draft of the manuscript; S.B., V.L. and F.McK. analysed the data; A.P., N.C., L.S., E.B. and B.F. reviewed plain language summaries and completed detailed tolerability surveys. The expert scientific committee included S.B., V.L., D.T., R.K., C.S., W.R., A.L., B.T., L.S., G.G., J.L.-S., S.H. and T.H. All authors revised and approved the final manuscript., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)