doi:10.1016/j.virs.2025.01.003

Ahmad, A., Eze, K., Noulin, N., Horvathova, V., Murray, B., Baillet, M., Grey, L., Mori, J.,Adda, N., 2022. EDP-938, a Respiratory Syncytial Virus Inhibitor, in a Human Virus Challenge. N Engl J Med, 386, 655-666.
Bailly, B., Richard, C.A., Sharma, G., Wang, L., Johansen, L., Cao, J., Pendharkar, V., Sharma, D.C., Galloux, M., Wang, Y., Cui, R., Zou, G., Guillon, P., Von Itzstein, M., Eleouet, J.F.,Altmeyer, R., 2016. Targeting human respiratory syncytial virus transcription anti-termination factor M2-1 to inhibit in vivo viral replication. Sci Rep, 6, 25806.
Behera, A.K., Matsuse, H., Kumar, M., Kong, X., Lockey, R.F.,Mohapatra, S.S., 2001. Blocking intercellular adhesion molecule-1 on human epithelial cells decreases respiratory syncytial virus infection. Biochem Biophys Res Commun, 280, 188-195.
Blockus, S., Sake, S.M., Wetzke, M., Grethe, C., Graalmann, T., Pils, M., Le Goffic, R., Galloux, M., Prochnow, H., Rox, K., et al., 2020. Labyrinthopeptins as virolytic inhibitors of respiratory syncytial virus cell entry. Antiviral Res, 177, 104774.
Brookes, D.W., Coates, M., Allen, H., Daly, L., Constant, S., Huang, S., Hows, M., Davis, A., Cass, L., Ayrton, J., Knowles, I., Strong, P., Rapeport, G.,Ito, K., 2018. Late therapeutic intervention with a respiratory syncytial virus L-protein polymerase inhibitor, PC786, on respiratory syncytial virus infection in human airway epithelium. Br J Pharmacol, 175, 2520-2534.
Coates, M., Brookes, D., Kim, Y.I., Allen, H., Fordyce, E.a.F., Meals, E.A., Colley, T., Ciana, C.L., Parra, G.F., Sherbukhin, V., et al., 2017. Preclinical Characterization of PC786, an Inhaled Small-Molecule Respiratory Syncytial Virus L Protein Polymerase Inhibitor. Antimicrob Agents Chemother, 61, e00737.-00717.
Cockerill, G.S., Angell, R.M., Bedernjak, A., Chuckowree, I., Fraser, I., Gascon-Simorte, J., Gilman, M.S.A., Good, J.a.D., Harland, R., Johnson, S.M., et al., 2021. Discovery of Sisunatovir (RV521), an Inhibitor of Respiratory Syncytial Virus Fusion. J Med Chem, 64, 3658-3676.
Cox, R.M., Toots, M., Yoon, J.J., Sourimant, J., Ludeke, B., Fearns, R., Bourque, E., Patti, J., Lee, E., Vernachio, J.,Plemper, R.K., 2018. Development of an allosteric inhibitor class blocking RNA elongation by the respiratory syncytial virus polymerase complex. J Biol Chem, 293, 16761-16777.
Currier, M.G., Lee, S., Stobart, C.C., Hotard, A.L., Villenave, R., Meng, J., Pretto, C.D., Shields, M.D., Nguyen, M.T., Todd, S.O., Chi, M.H., Hammonds, J., Krumm, S.A., Spearman, P., Plemper, R.K., Sakamoto, K., Peebles, R.S., Jr., Power, U.F.,Moore, M.L., 2016. EGFR Interacts with the Fusion Protein of Respiratory Syncytial Virus Strain 2-20 and Mediates Infection and Mucin Expression. PLoS Pathog, 12, e1005622.
Devincenzo, J., Tait, D., Efthimiou, J., Mori, J., Kim, Y.I., Thomas, E., Wilson, L., Harland, R., Mathews, N., Cockerill, S., Powell, K.,Littler, E., 2020. A Randomized, Placebo-Controlled, Respiratory Syncytial Virus Human Challenge Study of the Antiviral Efficacy, Safety, and Pharmacokinetics of RV521, an Inhibitor of the RSV-F Protein. Antimicrob Agents Chemother, 64, e01884.-01819.
Devincenzo, J., Cass, L., Murray, A., Woodward, K., Meals, E., Coates, M., Daly, L., Wheeler, V., Mori, J., Brindley, C., Davis, A., Mccurdy, M., Ito, K., Murray, B., Strong, P.,Rapeport, G., 2022. Safety and Antiviral Effects of Nebulized PC786 in a Respiratory Syncytial Virus Challenge Study. J Infect Dis, 225, 2087-2096.
Drysdale, S.B., Cathie, K., Flamein, F., Knuf, M., Collins, A.M., Hill, H.C., Kaiser, F., Cohen, R., Pinquier, D., Felter, C.T., et al., 2023. Nirsevimab for Prevention of Hospitalizations Due to RSV in Infants. N Engl J Med, 389, 2425-2435.
El Saleeby, C.M., Bush, A.J., Harrison, L.M., Aitken, J.A.,Devincenzo, J.P., 2011. Respiratory syncytial virus load, viral dynamics, and disease severity in previously healthy naturally infected children. J Infect Dis, 204, 996-1002.
Falsey, A.R., Hennessey, P.A., Formica, M.A., Cox, C.,Walsh, E.E., 2005. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med, 352, 1749-1759.
Fearns, R.,Deval, J., 2016. New antiviral approaches for respiratory syncytial virus and other mononegaviruses: Inhibiting the RNA polymerase. Antiviral Res, 134, 63-76.
Feldman, S.A., Hendry, R.M.,Beeler, J.A., 1999. Identification of a linear heparin binding domain for human respiratory syncytial virus attachment glycoprotein G. J Virol, 73, 6610-6617.
Ferir, G., Petrova, M.I., Andrei, G., Huskens, D., Hoorelbeke, B., Snoeck, R., Vanderleyden, J., Balzarini, J., Bartoschek, S., Bronstrup, M., Sussmuth, R.D.,Schols, D., 2013. The lantibiotic peptide labyrinthopeptin A1 demonstrates broad anti-HIV and anti-HSV activity with potential for microbicidal applications. PLoS One, 8, e64010.
Filardo, S., Di Pietro, M., Mastromarino, P.,Sessa, R., 2020. Therapeutic potential of resveratrol against emerging respiratory viral infections. Pharmacol Ther, 214, 107613.
Fleming-Dutra, K.E., Jones, J.M., Roper, L.E., Prill, M.M., Ortega-Sanchez, I.R., Moulia, D.L., Wallace, M., Godfrey, M., Broder, K.R., Tepper, N.K., Brooks, O., Sanchez, P.J., Kotton, C.N., Mahon, B.E., Long, S.S.,Mcmorrow, M.L., 2023. Use of the Pfizer Respiratory Syncytial Virus Vaccine During Pregnancy for the Prevention of Respiratory Syncytial Virus-Associated Lower Respiratory Tract Disease in Infants: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023. MMWR Morb Mortal Wkly Rep, 72, 1115-1122.
Garcia-Maurino, C., Moore-Clingenpeel, M., Thomas, J., Mertz, S., Cohen, D.M., Ramilo, O.,Mejias, A., 2019. Viral Load Dynamics and Clinical Disease Severity in Infants With Respiratory Syncytial Virus Infection. J Infect Dis, 219, 1207-1215.
Gilman, M.S.A., Liu, C., Fung, A., Behera, I., Jordan, P., Rigaux, P., Ysebaert, N., Tcherniuk, S., Sourimant, J., Eleouet, J.F., Sutto-Ortiz, P., Decroly, E., Roymans, D., Jin, Z.,Mclellan, J.S., 2019. Structure of the Respiratory Syncytial Virus Polymerase Complex. Cell, 179, 193-204 e114.
Hammitt, L.L., Dagan, R., Yuan, Y., Baca Cots, M., Bosheva, M., Madhi, S.A., Muller, W.J., Zar, H.J., Brooks, D., Grenham, A., Wahlby Hamren, U., Mankad, V.S., Ren, P., Takas, T., Abram, M.E., Leach, A., Griffin, M.P., Villafana, T.,Group, M.S., 2022. Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants. N Engl J Med, 386, 837-846.
Hasegawa, K., Jartti, T., Mansbach, J.M., Laham, F.R., Jewell, A.M., Espinola, J.A., Piedra, P.A.,Camargo, C.A., Jr., 2015. Respiratory syncytial virus genomic load and disease severity among children hospitalized with bronchiolitis: multicenter cohort studies in the United States and Finland. J Infect Dis, 211, 1550-1559.
Holwerda, M., V'kovski, P., Wider, M., Thiel, V.,Dijkman, R., 2020. Identification of an Antiviral Compound from the Pandemic Response Box that Efficiently Inhibits SARS-CoV-2 Infection In Vitro. Microorganisms, 8, 1872.
Hu, M., Bogoyevitch, M.A.,Jans, D.A., 2020. Impact of Respiratory Syncytial Virus Infection on Host Functions: Implications for Antiviral Strategies. Physiol Rev, 100, 1527-1594.
Issmail, L., Ramsbeck, D., Jager, C., Henning, T., Kleinschmidt, M., Buchholz, M.,Grunwald, T., 2023. Identification and evaluation of a novel tribenzamide derivative as an inhibitor targeting the entry of the respiratory syncytial virus. Antiviral Res, 211, 105547.
Johnson, S., Oliver, C., Prince, G.A., Hemming, V.G., Pfarr, D.S., Wang, S.C., Dormitzer, M., O'grady, J., Koenig, S., Tamura, J.K., Woods, R., Bansal, G., Couchenour, D., Tsao, E., Hall, W.C.,Young, J.F., 1997. Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus. J Infect Dis, 176, 1215-1224.
Jones, J.M., Fleming-Dutra, K.E., Prill, M.M., Roper, L.E., Brooks, O., Sanchez, P.J., Kotton, C.N., Mahon, B.E., Meyer, S., Long, S.S.,Mcmorrow, M.L., 2023. Use of Nirsevimab for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023. MMWR Morb Mortal Wkly Rep, 72, 920-925.
Le Rouzic, A., Fix, J., Vinck, R., Kappler-Gratias, S., Volmer, R., Gallardo, F., Eleouet, J.F., Keck, M., Cintrat, J.C., Barbier, J., Gillet, D.,Galloux, M., 2023. A New Derivative of Retro-2 Displays Antiviral Activity against Respiratory Syncytial Virus. Int J Mol Sci, 25, 415.
R. E. Levene, M.H.J. R, N. V. Mcallister, N. Bisht, J. S. Gibbons, J. Yu, T. J. Mann, A. Szymaniak, K. Mcgrath, I. Kim, L. Jiang, Y. S. Or, and B. Goodwin. 2022. In Vivo Efficacy of EDP-323, A Novel L-Protein Inhibitor, for the Treatment of Respiratory Syncytial Virus [Online]. Enanta Pharmaceuticals. Available: https://www.enanta.com/wp-content/uploads/2022/09/Levene_RSV2022_v13_FINAL.pdf [Accessed on 5 August 2024].
Micha Levi, P.D., Clinical Pharmacology and Pharmacometrics Leader, Joleen T White, P.D., Head of Bioassay Development and Operations 2022. Implementing a patient-centric sampling strategy in the global clinical development of RSM01 (Anti-RSV mAb) [Online]. Bill & Melinda Gates Medical Research Institute. Available: https://www.gatesmri.org/wp-content/uploads/2024/02/rsm01-world-congress-clinical-pharmacology.pdf [Accessed on 5 August 2024].
Micha Levi, S.W., Aparna B Anderson, Dale Taylor, Joleen T White, Luisa M Stamm, and Michael W Dunne, 2023. Pharmacokinetics and Safety in Healthy Adults of RSM01, a Novel RSV Monoclonal Antibody, and Population PK Modeling to Support Pediatric Development. Open Forum Infectious Diseases, 10, ofad500.453.
Lo, M.K., Jordan, R., Arvey, A., Sudhamsu, J., Shrivastava-Ranjan, P., Hotard, A.L., Flint, M., Mcmullan, L.K., Siegel, D., Clarke, M.O., Mackman, R.L., Hui, H.C., Perron, M., Ray, A.S., Cihlar, T., Nichol, S.T.,Spiropoulou, C.F., 2017. GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses. Sci Rep, 7, 43395.
Lo, M.K., Feldmann, F., Gary, J.M., Jordan, R., Bannister, R., Cronin, J., Patel, N.R., Klena, J.D., Nichol, S.T., Cihlar, T., Zaki, S.R., Feldmann, H., Spiropoulou, C.F.,De Wit, E., 2019. Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge. Sci Transl Med, 11, eaau9242.
Maas, B.M., Lommerse, J., Plock, N., Railkar, R.A., Cheung, S.Y.A., Caro, L., Chen, J., Liu, W., Zhang, Y., Huang, Q., et al., 2021. Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis. EBioMedicine, 73, 103651.
Mackman, R.L., Hui, H.C., Perron, M., Murakami, E., Palmiotti, C., Lee, G., Stray, K., Zhang, L., Goyal, B., Chun, K., et al., 2021. Prodrugs of a 1'-CN-4-Aza-7,9-dideazaadenosine C-Nucleoside Leading to the Discovery of Remdesivir (GS-5734) as a Potent Inhibitor of Respiratory Syncytial Virus with Efficacy in the African Green Monkey Model of RSV. J Med Chem, 64, 5001-5017.
Mcginley, J.P., Lin, G.L., Oner, D., Golubchik, T., O'connor, D., Snape, M.D., Gruselle, O., Langedijk, A.C., Wildenbeest, J., Openshaw, P., Nair, H., Aerssens, J., Bont, L., Martinon-Torres, F., Drysdale, S.B., Pollard, A.J.,Investigators, R., 2022. Clinical and Viral Factors Associated With Disease Severity and Subsequent Wheezing in Infants With Respiratory Syncytial Virus Infection. J Infect Dis, 226, S45-S54.
Mclellan, J.S., Chen, M., Leung, S., Graepel, K.W., Du, X., Yang, Y., Zhou, T., Baxa, U., Yasuda, E., Beaumont, T., Kumar, A., Modjarrad, K., Zheng, Z., Zhao, M., Xia, N., Kwong, P.D.,Graham, B.S., 2013. Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Science, 340, 1113-1117.
Melgar, M., Britton, A., Roper, L.E., Talbot, H.K., Long, S.S., Kotton, C.N.,Havers, F.P., 2023. Use of Respiratory Syncytial Virus Vaccines in Older Adults: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023. MMWR Morb Mortal Wkly Rep, 72, 793-801.
Kimberly Mills, P.J.D., Md ; Patrick Yao, Do ; Michael H. J. Rhodin, Phd, Scott Rottinghaus, Md, Alaa Ahmad, Phd. 2023. EDP-323, a First-in-Class, Once-Daily, Oral L-Protein Inhibitor for the Treatment of RSV: Results from a Phase 1 Study in Healthy Subjects and Correlation with In Vitro Antiviral Activity [Online]. Enanta Pharmaceuticals. Available: https://www.enanta.com/wp-content/uploads/2023/09/EDP-323-001-ESWI-Poster-presentation_FINAL.pdf [Accessed on 5 August 2024].
Nelson, C.D., Carney, D.W., Derdowski, A., Lipovsky, A., Gee, G.V., O'hara, B., Williard, P., Dimaio, D., Sello, J.K.,Atwood, W.J., 2013. A retrograde trafficking inhibitor of ricin and Shiga-like toxins inhibits infection of cells by human and monkey polyomaviruses. mBio, 4, e00729.-00713.
Openshaw, P.J.M., Chiu, C., Culley, F.J.,Johansson, C., 2017. Protective and Harmful Immunity to RSV Infection. Annu Rev Immunol, 35, 501-532.
Rhodin, M.H.J., Mcallister, N.V., Castillo, J., Noton, S.L., Fearns, R., Kim, I.J., Yu, J., Blaisdell, T.P., Panarese, J., Shook, B.C., Or, Y.S., Goodwin, B.,Lin, K., 2021. EDP-938, a novel nucleoprotein inhibitor of respiratory syncytial virus, demonstrates potent antiviral activities in vitro and in a non-human primate model. PLoS Pathog, 17, e1009428.
M. H. J. Rhodin, N.V. M., N. Bisht, R. E. Levene, J. S. Gibbons, A. Balakrishnan, J. Yu, A. A. Szymaniak, K. P. Mcgrath, T. J. Mann, I. J. Kim, B. Ludeke, R. Fearns, Y. S. Or, and B. Goodwin. 2022 Oct 19. EDP-323, a Small Molecule L-Protein Inhibitor in Development Against Respiratory Syncytial Virus. [Online]. Enanta Pharmaceuticals. Available: https://www.enanta.com/wp-content/uploads/2022/10/EDP-323-RSV22-Final-1.pdf [Accessed on 5 August 2024].
Risso-Ballester, J., Galloux, M., Cao, J., Le Goffic, R., Hontonnou, F., Jobart-Malfait, A., Desquesnes, A., Sake, S.M., Haid, S., Du, M., Zhang, X., Zhang, H., Wang, Z., Rincheval, V., Zhang, Y., Pietschmann, T., Eleouet, J.F., Rameix-Welti, M.A.,Altmeyer, R., 2021. A condensate-hardening drug blocks RSV replication in vivo. Nature, 595, 596-599.
Russell, C.D., Unger, S.A., Walton, M.,Schwarze, J., 2017. The Human Immune Response to Respiratory Syncytial Virus Infection. Clin Microbiol Rev, 30, 481-502.
Sake, S.M., Zhang, X., Rajak, M.K., Urbanek-Quaing, M., Carpentier, A., Gunesch, A.P., Grethe, C., Matthaei, A., Ruckert, J., Galloux, M., et al., 2024. Drug repurposing screen identifies lonafarnib as respiratory syncytial virus fusion protein inhibitor. Nat Commun, 15, 1173.
Scheltema, N.M., Gentile, A., Lucion, F., Nokes, D.J., Munywoki, P.K., Madhi, S.A., Groome, M.J., Cohen, C., Moyes, J., Thorburn, K., et al., 2017. Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series. Lancet Glob Health, 5, e984-e991.
Shi, T., Mcallister, D.A., O'brien, K.L., Simoes, E.a.F., Madhi, S.A., Gessner, B.D., Polack, F.P., Balsells, E., Acacio, S., Aguayo, C., et al., 2017. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet, 390, 946-958.
Shtanko, O., Sakurai, Y., Reyes, A.N., Noel, R., Cintrat, J.C., Gillet, D., Barbier, J.,Davey, R.A., 2018. Retro-2 and its dihydroquinazolinone derivatives inhibit filovirus infection. Antiviral Res, 149, 154-163.
Sivan, G., Weisberg, A.S., Americo, J.L.,Moss, B., 2016. Retrograde Transport from Early Endosomes to the trans-Golgi Network Enables Membrane Wrapping and Egress of Vaccinia Virus Virions. J Virol, 90, 8891-8905.
Sourimant, J., Lieber, C.M., Yoon, J.J., Toots, M., Govindarajan, M., Udumula, V., Sakamoto, K., Natchus, M.G., Patti, J., Vernachio, J.,Plemper, R.K., 2022. Orally efficacious lead of the AVG inhibitor series targeting a dynamic interface in the respiratory syncytial virus polymerase. Sci Adv, 8, eabo2236.
Tang, A., Chen, Z., Cox, K.S., Su, H.P., Callahan, C., Fridman, A., Zhang, L., Patel, S.B., Cejas, P.J., Swoyer, R., et al., 2019. A potent broadly neutralizing human RSV antibody targets conserved site IV of the fusion glycoprotein. Nat Commun, 10, 4153.
Tayyari, F., Marchant, D., Moraes, T.J., Duan, W., Mastrangelo, P.,Hegele, R.G., 2011. Identification of nucleolin as a cellular receptor for human respiratory syncytial virus. Nat Med, 17, 1132-1135.
Tripp, R.A., Jones, L.P., Haynes, L.M., Zheng, H., Murphy, P.M.,Anderson, L.J., 2001. CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein. Nat Immunol, 2, 732-738.
Walsh, E.E.,Hruska, J., 1983. Monoclonal antibodies to respiratory syncytial virus proteins: identification of the fusion protein. J Virol, 47, 171-177.
Warren, T.K., Jordan, R., Lo, M.K., Ray, A.S., Mackman, R.L., Soloveva, V., Siegel, D., Perron, M., Bannister, R., Hui, H.C., et al., 2016. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature, 531, 381-385.
Wilkins, D., Langedijk, A.C., Lebbink, R.J., Morehouse, C., Abram, M.E., Ahani, B., Aksyuk, A.A., Baraldi, E., Brady, T., Chen, A.T., et al., 2023. Nirsevimab binding-site conservation in respiratory syncytial virus fusion glycoprotein worldwide between 1956 and 2021: an analysis of observational study sequencing data. Lancet Infect Dis, 23, 856-866.
Xie, Y., Yin, W., Zhang, Y., Shang, W., Wang, Z., Luan, X., Tian, G., Aisa, H.A., Xu, Y., Xiao, G., Li, J., Jiang, H., Zhang, S., Zhang, L., Xu, H.E.,Shen, J., 2021. Design and development of an oral remdesivir derivative VV116 against SARS-CoV-2. Cell Res, 31, 1212-1214.
Xiong, Y., Tao, K., Li, T., Ou, W., Zhou, Y., Zhang, W., Wang, S., Qi, R.,Ji, J., 2024. Resveratrol inhibits respiratory syncytial virus replication by targeting heparan sulfate proteoglycans. Food Funct, 15, 1948-1962.
Yoshida, I., Arikawa, K., Honma, Y., Inatani, S., Yoshinaga, M.,Sugiyama, H., 2020. Pharmacological Characterization of TP0591816, a Novel Macrocyclic Respiratory Syncytial Virus Fusion Inhibitor with Antiviral Activity against F Protein Mutants. Antimicrob Agents Chemother, 65, e01407.-01420.
Zhang, R., Zhang, Y., Zheng, W., Shang, W., Wu, Y., Li, N., Xiong, J., Jiang, H., Shen, J., Xiao, G., Xie, Y.,Zhang, L., 2022. Oral remdesivir derivative VV116 is a potent inhibitor of respiratory syncytial virus with efficacy in mouse model. Signal Transduct Target Ther, 7, 123.
Zheng, X., Gao, L., Wang, L., Liang, C., Wang, B., Liu, Y., Feng, S., Zhang, B., Zhou, M., Yu, X., Xiang, K., Chen, L., Guo, T., Shen, H.C., Zou, G., Wu, J.Z.,Yun, H., 2019. Discovery of Ziresovir as a Potent, Selective, and Orally Bioavailable Respiratory Syncytial Virus Fusion Protein Inhibitor. J Med Chem, 62, 6003-6014.