Vaccine and therapeutic agents against the respiratory syncytial virus: resolved and unresolved issue

Abstract

Respiratory syncytial virus (RSV) is a predominant pathogen responsible for respiratory tract infections among infants, the elderly, and immunocompromised individuals. In recent years, significant progress has been made in innovative vaccines and therapeutic agents targeting RSV. Nevertheless, numerous challenges and bottlenecks persist in the prevention and treatment of RSV infections. This review will provide an overview of the resolved and unresolved issues surrounding the development of vaccines and therapeutic agents against RSV. As of September 2024, three RSV vaccines against acute lower respiratory infections (ALRI) have been approved globally. Additionally, there have been notable progress in the realm of passive immunoprophylactic antibodies, with the monoclonal antibody nirsevimab receiving regulatory approval for the prevention of RSV infections in infants. Furthermore, a variety of RSV therapeutic agents are currently under clinical investigation, with the potential to yield breakthrough advancements in the foreseeable future. This review delineates the advancements and challenges faced in vaccines and therapeutic agents targeting RSV. It aims to provide insights that will guide the development of effective preventive and control measures for RSV.

Keywords

nirsevimab / palivizumab / prefusion protein / respiratory syncytial virus / structure-based vaccine / ziresovir

References

[1] Borchers AT, Chang C, Gershwin ME, Gershwin LJ. Respiratory syncytial virus–a comprehensive review. Clin Rev Allergy Immunol. 2013; 45(3): 331-379.

[2] Griffiths C, Drews SJ, Marchant DJ. Respiratory syncytial virus: infection, detection, and new options for prevention and treatment. Clin Microbiol Rev. 2017; 30(1): 277-319.

[3] Coultas JA, Smyth R, Openshaw PJ. Respiratory syncytial virus (RSV): a scourge from infancy to old age. Thorax. 2019; 74(10): 986-993.

[4] Li Y, Wang X, Blau DM, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis. Lancet. 2022; 399(10340): 2047-2064.

[5] Haber N. Respiratory syncytial virus infection in elderly adults. Med Mal Infect. 2018; 48(6): 377-382.

[6] Shi T, Denouel A, Tietjen AK, et al. Global disease burden estimates of respiratory syncytial virus-associated acute respiratory infection in older adults in 2015: a systematic review and meta-analysis. J Infect Dis. 2020; 222: S577-S583. Suppl 7.

[7] Pangesti KNA, Abd El Ghany M, Walsh MG, Kesson AM, Hill-Cawthorne GA. Molecular epidemiology of respiratory syncytial virus. Rev Med Virol. 2018; 28(2): 10.1002/rmv.

[8] Obando-Pacheco P, Justicia-Grande AJ, Rivero-Calle I, et al. Respiratory syncytial virus seasonality: a global overview. J Infect Dis. 2018; 217(9): 1356-1364.

[9] Pandya MC, Callahan SM, Savchenko KG, Stobart CC. A contemporary view of respiratory syncytial virus (RSV) biology and strain-specific differences. Pathogens. 2019; 8(2): 67.

[10] McLellan JS, Ray WC, Peeples ME. Structure and function of respiratory syncytial virus surface glycoproteins. Curr Top Microbiol Immunol. 2013; 372: 83-104.

[11] Anderson LJ, Jadhao SJ, Paden CR, Tong S. Functional features of the respiratory syncytial virus G protein. Viruses. 2021; 13(7): 1214.

[12] Cadena-Cruz C, Villarreal Camacho JL, De Avila-Arias M, Hurtado-Gomez L, Rodriguez A, San-Juan-Vergara H. Respiratory syncytial virus entry mechanism in host cells: a general overview. Mol Microbiol. 2023; 120(3): 341-350.

[13] Griffiths CD, Bilawchuk LM, McDonough JE, et al. IGF1R is an entry receptor for respiratory syncytial virus. Nature. 2020; 583(7817): 615-619.

[14] McLellan JS, Chen M, Leung S, et al. Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Science. 2013; 340(6136): 1113-1117.

[15] Lee Y, Klenow L, Coyle EM, Grubbs G, Golding H, Khurana S. Monoclonal antibodies targeting sites in respiratory syncytial virus attachment G protein provide protection against RSV-A and RSV-B in mice. Nat Commun. 2024; 15(1): 2900.

[16] Abd-Eldaim MM, Maarouf M, Potgieter L, Kania SA. Amino acid variations of the immuno-dominant domain of respiratory syncytial virus attachment glycoprotein (G) affect the antibody responses In BALB/c mice. J Virol Methods. 2023; 316: 114712.

[17] Bergeron HC, Murray J, Nunez Castrejon AM, DuBois RM, Tripp RA. Respiratory syncytial virus (RSV) G protein vaccines with central conserved domain mutations induce CX3C-CX3CR1 blocking antibodies. Viruses. 2021; 13(2): 352.

[18] Mazur NI, Terstappen J, Baral R, et al. Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape. Lancet Infect Dis. 2023; 23(1): e2-e21.

[19] Crank MC, Ruckwardt TJ, Chen M, et al. A proof of concept for structure-based vaccine design targeting RSV in humans. Science. 2019; 365(6452): 505-509.

[20] Cao D, Gao Y, Roesler C, et al. Cryo-EM structure of the respiratory syncytial virus RNA polymerase. Nat Commun. 2020; 11(1): 368.

[21] Muniyandi S, Pangratiou G, Edwards TA, Barr JN. Structure and function of the human respiratory syncytial virus M2-1 protein. Subcell Biochem. 2018; 88: 245-260.

[22] Scudero OB, Santiago VF, Palmisano G, Simabuco FM, Ventura AM. The respiratory syncytial virus M2-2 protein is targeted for proteasome degradation and inhibits translation and stress granules assembly. PLoS One. 2023; 18(7): e0289100.

[23] Thornhill EM, Verhoeven D. Respiratory syncytial virus’s non-structural proteins: masters of interference. Front Cell Infect Microbiol. 2020; 10: 225.

[24] Merritt TN, Pei J, Leung DW. Pathogenicity and virulence of human respiratory syncytial virus: multifunctional nonstructural proteins NS1 and NS2. Virulence. 2023:2283897.

[25] Gatt D, Martin I, AlFouzan R, Moraes TJ. Prevention and treatment strategies for respiratory syncytial virus (RSV). Pathogens. 2023; 12(2): 154.

[26] Esposito S, Abu Raya B, Baraldi E, et al. RSV prevention in all infants: which is the most preferable strategy. Front Immunol. 2022; 13: 880368.

[27] Langedijk AC, Bont LJ. Respiratory syncytial virus infection and novel interventions. Nat Rev Microbiol. 2023; 21(11): 734-749.

[28] Shang Z, Tan S, Ma D. Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies. Int J Biol Sci. 2021; 17(14): 4073-4091.

[29] Topalidou X, Kalergis AM, Papazisis G. Respiratory syncytial virus vaccines: a review of the candidates and the approved vaccines. Pathogens. 2023; 12(10): 1259.

[30] Swathi M. Arexvy: a comprehensive review of the respiratory syncytial virus vaccine for revolutionary protection. Viral Immunol. 2024; 37(1): 12-15.

[31] In brief: RSV vaccine (Arexvy) for ages 50–59. Med Lett Drugs Ther. 2024; 66(1707): 113-114.

[32] Two vaccines (Arexvy and Abrysvo) for prevention of RSV disease. Med Lett Drugs Ther. 2023; 65(1686): 155-156.

[33] Shaukat A, Batool UEA, Nasser N. A new era in maternal-child health: abrysvo’s role in RSV prevention. Health Sci Rep. 2024; 7(7): e2236.

[34] Qiu X, Xu S, Lu Y, et al. Development of mRNA vaccines against respiratory syncytial virus (RSV). Cytokine Growth Factor Rev. 2022; 68: 37-53.

[35] Baraldi E, Checcucci Lisi G, Costantino C, et al. RSV disease in infants and young children: can we see a brighter future. Hum Vaccin Immunother. 2022; 18(4): 2079322.

[36] Garegnani L, Styrmisdottir L, Roson Rodriguez P, Escobar Liquitay CM, Esteban I, Franco JV. Palivizumab for preventing severe respiratory syncytial virus (RSV) infection in children. Cochrane Database Syst Rev. 2021; 11(11): CD013757.

[37] O’Hagan S, Galway N, Shields MD, Mallett P, Groves HE. Review of the safety, efficacy and tolerability of palivizumab in the prevention of severe respiratory syncytial virus (RSV) disease. Drug Healthc Patient Saf. 2023; 15: 103-112.

[38] El-Atawi K, De Luca D, Ramanathan R, et al. Efficacy and safety of palivizumab as a prophylaxis for respiratory syncytial virus (RSV) disease: an updated systemic review and meta-analysis. Cureus. 2023; 15(12): e51375.

[39] Keam SJ. Nirsevimab: first approval. Drugs. 2023; 83(2): 181-187.

[40] Balbi H. Nirsevimab: a review. Pediatr Allergy Immunol Pulmonol. 2024; 37(1): 3-6.

[41] Tejada S, Martinez-Reviejo R, Karakoc HN, Pena-Lopez Y, Manuel O, Rello J. Ribavirin for treatment of subjects with respiratory syncytial virus-related infection: a systematic review and meta-analysis. Adv Ther. 2022; 39(9): 4037-4051.

[42] Manothummetha K, Mongkolkaew T, Tovichayathamrong P, et al. Ribavirin treatment for respiratory syncytial virus infection in patients with haematologic malignancy and haematopoietic stem cell transplant recipients: a systematic review and meta-analysis. Clin Microbiol Infect. 2023; 29(10): 1272-1279.

[43] Drysdale SB, Barr RS, Rollier CS, Green CA, Pollard AJ, Sande CJ. Priorities for developing respiratory syncytial virus vaccines in different target populations. Sci Transl Med. 2020; 12(535): eaax2466.

[44] Miller RJ, Mousa JJ. Structural basis for respiratory syncytial virus and human metapneumovirus neutralization. Curr Opin Virol. 2023; 61: 101337.

[45] Mejias A, Rodriguez-Fernandez R, Oliva S, Peeples ME, Ramilo O. The journey to a respiratory syncytial virus vaccine. Ann Allergy Asthma Immunol. 2020; 125(1): 36-46.

[46] Patel N, Tian JH, Flores R, et al. Flexible RSV prefusogenic fusion glycoprotein exposes multiple neutralizing epitopes that may collectively contribute to protective immunity. Vaccines (Basel). 2020; 8(4): 607.

[47] Killikelly AM, Kanekiyo M, Graham BS. Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus. Sci Rep. 2016; 6: 34108.

[48] McLellan JS, Chen M, Joyce MG, et al. Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. Science. 2013; 342(6158): 592-598.

[49] Krarup A, Truan D, Furmanova-Hollenstein P, et al. A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism. Nat Commun. 2015; 6: 8143.

[50] Marcandalli J, Fiala B, Ols S, et al. Induction of potent neutralizing antibody responses by a designed protein nanoparticle vaccine for respiratory syncytial virus. Cell. 2019; 176(6): 1420-1431.

[51] McCool RS, Musayev M, Bush SM, et al. Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein elicits antibodies targeting a membrane-proximal epitope. J Virol. 2023; 97(10): e0092923.

[52] Che Y, Gribenko AV, Song X, et al. Rational design of a highly immunogenic prefusion-stabilized F glycoprotein antigen for a respiratory syncytial virus vaccine. Sci Transl Med. 2023; 15(693): eade6422.

[53] Ruckwardt TJ, Morabito KM, Phung E, et al. Safety, tolerability, and immunogenicity of the respiratory syncytial virus prefusion F subunit vaccine DS-Cav1: a phase 1, randomised, open-label, dose-escalation clinical trial. Lancet Respir Med. 2021; 9(10): 1111-1120.

[54] Ruckwardt TJ. The road to approved vaccines for respiratory syncytial virus. NPJ Vaccines. 2023; 8(1): 138.

[55] Openshaw PJ, Culley FJ, Olszewska W. Immunopathogenesis of vaccine-enhanced RSV disease. Vaccine. 2001; 20: S27-31. Suppl 1.

[56] Polack FP, Alvarez-Paggi D, Libster R, et al. Fatal enhanced respiratory syncytial virus disease in toddlers. Sci Transl Med. 2021; 13(616): eabj7843.

[57] Stobart CC, Rostad CA, Ke Z, et al. A live RSV vaccine with engineered thermostability is immunogenic in cotton rats despite high attenuation. Nat Commun. 2016; 7: 13916.

[58] Karron RA, Luongo C, Woods S, et al. Evaluation of the live-attenuated intranasal respiratory syncytial virus (RSV) vaccine RSV/6120/DeltaNS2/1030s in RSV-seronegative young children. J Infect Dis. 2024; 229(2): 346-354.

[59] McFarland EJ, Karron RA, Muresan P, et al. Live-attenuated respiratory syncytial virus vaccine candidate with deletion of RNA synthesis regulatory protein M2-2 is highly immunogenic in children. J Infect Dis. 2018; 217(9): 1347-1355.

[60] Cunningham CK, Karron RA, Muresan P, et al. Evaluation of recombinant live-attenuated respiratory syncytial virus (RSV) vaccines RSV/DeltaNS2/Delta1313/I1314L and RSV/276 in RSV-seronegative children. J Infect Dis. 2022; 226(12): 2069-2078.

[61] Chang LA, Phung E, Crank MC, et al. A prefusion-stabilized RSV F subunit vaccine elicits B cell responses with greater breadth and potency than a postfusion F vaccine. Sci Transl Med. 2022; 14(676): eade0424.

[62] Jares Baglivo S, Polack FP, The long road to protect infants against severe RSV lower respiratory tract illness. F1000Res. 2019; 8: F1000 Faculty Rev-610

[63] Li C, Zhou X, Zhong Y, et al. A recombinant g protein plus cyclosporine A-based respiratory syncytial virus vaccine elicits humoral and regulatory T cell responses against infection without vaccine-enhanced disease. J Immunol. 2016; 196(4): 1721-1731.

[64] Cheng X, Zhao G, Dong A, et al. A first-in-human trial to evaluate the safety and immunogenicity of a G protein-based recombinant respiratory syncytial virus vaccine in healthy adults 18–45 years of age. Vaccines (Basel). 2023; 11(5): 999.

[65] Jordan E, Kabir G, Schultz S, et al. Reduced respiratory syncytial virus load, symptoms, and infections: a human challenge trial of MVA-BN-RSV vaccine. J Infect Dis. 2023; 228(8): 999-1011.

[66] Samy N, Reichhardt D, Schmidt D, et al. Safety and immunogenicity of novel modified vaccinia Ankara-vectored RSV vaccine: a randomized phase I clinical trial. Vaccine. 2020; 38(11): 2608-2619.

[67] Jordan E, Lawrence SJ, Meyer TPH, et al. Broad antibody and cellular immune response from a phase 2 clinical trial with a novel multivalent poxvirus-based respiratory syncytial virus vaccine. J Infect Dis. 2021; 223(6): 1062-1072.

[68] Falsey AR, Williams K, Gymnopoulou E, et al. Efficacy and safety of an Ad26.RSV.preF-RSV preF protein vaccine in older adults. N Engl J Med. 2023; 388(7): 609-620.

[69] Comeaux CA, Bart S, Bastian AR, et al. Safety, immunogenicity, and regimen selection of Ad26.RSV.preF-based vaccine combinations: a randomized, double-blind, placebo-controlled, phase 1/2a study. J Infect Dis. 2024; 229(1): 19-29.

[70] Falsey AR, Hosman T, Bastian AR, et al. Long-term efficacy and immunogenicity of Ad26.RSV.preF-RSV preF protein vaccine (CYPRESS): a randomised, double-blind, placebo-controlled, phase 2b study. Lancet Infect Dis. 2024; 24(9): 1015-1024.

[71] Jastorff A, Bastian AR, Ligtenberg N, Klyashtornyy V, Callendret B, Heijnen E. Immunogenicity, safety and reactogenicity of Ad26.RSV.preF/RSV preF protein vaccine in adults aged 60 to 75 years: a comparison of phase 2b and phase 3 clinical trial material. Hum Vaccin Immunother. 2024; 20(1): 2383504.

[72] Shaw CA, Mithani R, Kapoor A, et al. Safety, tolerability and immunogenicity of a mrna-based rsv vaccine in healthy young adults in a phase 1 clinical trial. J Infect Dis. 2024; 230(3): e637-e646.

[73] Goswami J, Baqui AH, Doreski PA, et al. Humoral immunogenicity of mRNA-1345 RSV vaccine in older adults. J Infect Dis. 2024.

[74] Wilson E, Goswami J, Baqui AH, et al. Efficacy and safety of an mRNA-Based RSV PreF vaccine in older adults. N Engl J Med. 2023; 389(24): 2233-2244.

[75] Shaw CA, Essink B, Harper C, et al. Safety and immunogenicity of an mRNA-based RSV vaccine including a 12-month booster in a phase I clinical trial in healthy older adults. J Infect Dis. 2024; 230(3): e647-e656.

[76] Kampmann B, Madhi SA, Munjal I, et al. Bivalent prefusion F vaccine in pregnancy to prevent RSV illness in infants. N Engl J Med. 2023; 388(16): 1451-1464.

[77] Madhi SA, Polack FP, Piedra PA, et al. Respiratory syncytial virus vaccination during pregnancy and effects in infants. N Engl J Med. 2020; 383(5): 426-439.

[78] Sebghati M, Khalil A. Uptake of vaccination in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2021; 76: 53-65.

[79] Mazur NI, Horsley NM, Englund JA, et al. Breast milk prefusion F immunoglobulin G as a correlate of protection against respiratory syncytial virus acute respiratory illness. J Infect Dis. 2019; 219(1): 59-67.

[80] Parsons EL, Kim JS, Malloy AMW. Development of innate and adaptive immunity to RSV in young children. Cell Immunol. 2024:104824. 399-400.

[81] Chirkova T, Ha B, Rimawi BH, Oomens AGP, Hartert TV, Anderson LJ. In vitro model for the assessment of human immune responses to subunit RSV vaccines. PLoS One. 2020; 15(3): e0229660.

[82] Yu JR, Kim S, Lee JB, Chang J. Single intranasal immunization with recombinant adenovirus-based vaccine induces protective immunity against respiratory syncytial virus infection. J Virol. 2008; 82(5): 2350-2357.

[83] Schwarz TF, Hwang SJ, Ylisastigui P, et al. Immunogenicity and safety following 1 dose of AS01E-adjuvanted respiratory syncytial virus prefusion f protein vaccine in older adults: a phase 3 trial. J Infect Dis. 2024; 230(1): e102-e110.

[84] Papi A, Ison MG, Langley JM, et al. Respiratory syncytial virus prefusion f protein vaccine in older adults. N Engl J Med. 2023; 388(7): 595-608.

[85] Ison MG, Papi A, Athan E, et al. Efficacy and safety of respiratory syncytial virus (RSV) prefusion f protein vaccine (RSVPreF3 OA) in older adults over 2 RSV seasons. Clin Infect Dis. 2024; 78(6): 1732-1744.

[86] Ferguson M, Schwarz TF, Nunez SA, et al. Noninferior immunogenicity and consistent safety of respiratory syncytial virus prefusion f protein vaccine in adults 50–59 Years Compared to >/= 60 Years of Age. Clin Infect Dis. 2024; 79(4): 1074-1084.

[87] Nodelman M, Scott AM. RSVpreF (Abrysvo) and nirsevimab-alip (Beyfortus) for the prevention of respiratory syncytial virus infection. Am Fam Physician. 2024; 109(6): 578-579.

[88] Baber J, Arya M, Moodley Y, et al. A phase 1/2 study of a respiratory syncytial virus prefusion f vaccine with and without adjuvant in healthy older adults. J Infect Dis. 2022; 226(12): 2054-2063.

[89] Schmoele-Thoma B, Zareba AM, Jiang Q, et al. Vaccine efficacy in adults in a respiratory syncytial virus challenge study. N Engl J Med. 2022; 386(25): 2377-2386.

[90] Walsh EE, Perez Marc G, Zareba AM, et al. Efficacy and safety of a bivalent RSV prefusion f vaccine in older adults. N Engl J Med. 2023; 388(16): 1465-1477.

[91] Fleming-Dutra KE, Jones JM, Roper LE, et al. 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. 2023; 72(41): 1115-1122.

[92] Syed YY. Respiratory syncytial virus prefusion f subunit vaccine: first approval of a maternal vaccine to protect infants. Paediatr Drugs. 2023; 25(6): 729-734.

[93] Simoes EAF, Center KJ, Tita ATN, et al. Prefusion F protein-based respiratory syncytial virus immunization in pregnancy. N Engl J Med. 2022; 386(17): 1615-1626.

[94] Groppo R, DiNapoli J, Il Jeong K, et al. Effect of genetic background and delivery route on the preclinical properties of a live attenuated RSV vaccine. PLoS One. 2018; 13(6): e0199452.

[95] McFarland EJ, Karron RA, Muresan P, et al. Live-attenuated respiratory syncytial virus vaccine with M2-2 deletion and with small hydrophobic noncoding region is highly immunogenic in children. J Infect Dis. 2020; 221(12): 2050-2059.

[96] Alamares-Sapuay J, Kishko M, Lai C, et al. Mutations in the F protein of the live-attenuated respiratory syncytial virus vaccine candidate DeltaNS2/Delta1313/I1314L increase the stability of infectivity and content of prefusion F protein. PLoS One. 2024; 19(4): e0301773.

[97] Le Nouen C, McCarty T, Brown M, et al. Genetic stability of genome-scale deoptimized RNA virus vaccine candidates under selective pressure. Proc Natl Acad Sci USA. 2017; 114(3): E386-E395.

[98] Mueller S, Stauft CB, Kalkeri R, et al. A codon-pair deoptimized live-attenuated vaccine against respiratory syncytial virus is immunogenic and efficacious in non-human primates. Vaccine. 2020; 38(14): 2943-2948.

[99] Muralidharan A, Li C, Wang L, Li X. Immunopathogenesis associated with formaldehyde-inactivated RSV vaccine in preclinical and clinical studies. Expert Rev Vaccines. 2017; 16(4): 351-360.

[100] Acosta PL, Caballero MT, Polack FP. Brief history and characterization of enhanced respiratory syncytial virus disease. Clin Vaccine Immunol. 2015; 23(3): 189-195.

[101] Buchholz UJ, Cunningham CK, Muresan P, et al. Live respiratory syncytial virus (RSV) vaccine candidate containing stabilized temperature-sensitivity mutations is highly attenuated in RSV-seronegative infants and children. J Infect Dis. 2018; 217(9): 1338-1346.

[102] Karron RA, Luongo C, Mateo JS, Wanionek K, Collins PL, Buchholz UJ. Safety and immunogenicity of the respiratory syncytial virus vaccine RSV/DeltaNS2/Delta1313/I1314L in RSV-seronegative children. J Infect Dis. 2020; 222(1): 82-91.

[103] McFarland EJ, Karron RA, Muresan P, et al. Live respiratory syncytial virus attenuated by M2-2 deletion and stabilized temperature sensitivity mutation 1030s is a promising vaccine candidate in children. J Infect Dis. 2020; 221(4): 534-543.

[104] Kingwell K. RSV vaccines score landmark FDA approvals. Nat Rev Drug Discov. 2023; 22(7): 523-525.

[105] Houle SKD, Andrew MK. RSV vaccination in older adults: addressing vaccine hesitancy using the 3C model. Can Pharm J (Ott). 2024; 157(1): 39-44.

[106] Frenkel LD, Gaur S, Bellanti JA. The third pandemic: the respiratory syncytial virus landscape and specific considerations for the allergist/immunologist. Allergy Asthma Proc. 2023; 44(4): 220-228.

[107] Dieussaert I, Hyung Kim J, Luik S, et al. RSV prefusion F protein-based maternal vaccine—preterm birth and other outcomes. N Engl J Med. 2024; 390(11): 1009-1021.

[108] Rasmussen SA, Jamieson DJ. Maternal RSV vaccine—weighing benefits and risks. N Engl J Med. 2024; 390(11): 1050-1051.

[109] Otsuki T, Akada S, Anami A, et al. Efficacy and safety of bivalent RSVpreF maternal vaccination to prevent RSV illness in Japanese infants: subset analysis from the pivotal randomized phase 3 MATISSE trial. Vaccine. 2024; 42(22): 126041.

[110] Leroux-Roels I, Van Ranst M, Vandermeulen C, et al. Safety and immunogenicity of a revaccination with a respiratory syncytial virus prefusion f vaccine in older adults: a phase 2b study. J Infect Dis. 2024; 229(2): 355-366.

[111] Isaacs A, Li Z, Cheung STM, et al. Adjuvant selection for influenza and RSV prefusion subunit vaccines. Vaccines (Basel). 2021; 9(2): 71.

[112] Leroux-Roels I, Davis MG, Steenackers K, et al. Safety and immunogenicity of a respiratory syncytial virus prefusion F (RSVPreF3) candidate vaccine in older adults: phase 1/2 randomized clinical trial. J Infect Dis. 2023; 227(6): 761-772.

[113] Walsh EE, Falsey AR, Scott DA, et al. A randomized phase 1/2 study of a respiratory syncytial virus prefusion F vaccine. J Infect Dis. 2022; 225(8): 1357-1366.

[114] Taylor G. Animal models of respiratory syncytial virus infection. Vaccine. 2017; 35(3): 469-480.

[115] Harder OE, Niewiesk S. Respiratory syncytial virus infection modeled in aging cotton rats (Sigmodon hispidus) and mice (Mus musculus). Adv Virol. 2022; 2022: 8637545.

[116] Gilbert PB, Fong Y, Hejazi NS, et al. Four statistical frameworks for assessing an immune correlate of protection (surrogate endpoint) from a randomized, controlled, vaccine efficacy trial. Vaccine. 2024; 42(9): 2181-2190.

[117] Trombetta CM, Montomoli E. Influenza immunology evaluation and correlates of protection: a focus on vaccines. Expert Rev Vaccines. 2016; 15(8): 967-976.

[118] Lambkin-Williams R, Noulin N, Mann A, Catchpole A, Gilbert AS. The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics. Respir Res. 2018; 19(1): 123.

[119] Ahmad A, Eze K, Noulin N, et al. EDP-938, a respiratory syncytial virus inhibitor, in a human virus challenge. N Engl J Med. 2022; 386(7): 655-666.

[120] Nuttens C, Moyersoen J, Curcio D, et al. Differences between RSV A and RSV B subgroups and implications for pharmaceutical preventive measures. Infect Dis Ther. 2024; 13(8): 1725-1742.

[121] Kopera E, Czajka H, Zapolnik P, Mazur A. New insights on respiratory syncytial virus prevention. Vaccines (Basel). 2023; 11(12).

[122] Falsey AR, Walsh EE, Scott DA, et al. Phase 1/2 randomized study of the immunogenicity, safety, and tolerability of a respiratory syncytial virus prefusion F vaccine in adults with concomitant inactivated influenza vaccine. J Infect Dis. 2022; 225(12): 2056-2066.

[123] Chandler R, Montenegro N, Llorach C, et al. Immunogenicity, reactogenicity, and safety of AS01E-adjuvanted RSV prefusion F protein-based candidate vaccine (RSVPreF3 OA) when co-administered with a seasonal quadrivalent influenza vaccine in older adults: results of a phase 3, open-label, randomized controlled trial. Clin Infect Dis. 2024:ciad786.

[124] Athan E, Baber J, Quan K, et al. Safety and immunogenicity of bivalent RSVpreF vaccine coadministered with seasonal inactivated influenza vaccine in older adults. Clin Infect Dis. 2024; 78(5): 1360-1368.

[125] Spearman P, Jin H, Knopp K, et al. Intranasal parainfluenza virus type 5 (PIV5)-vectored RSV vaccine is safe and immunogenic in healthy adults in a phase 1 clinical study. Sci Adv. 2023; 9(43): eadj7611.

[126] Wandstrat TL. Respiratory syncytial virus immune globulin intravenous. Ann Pharmacother. 1997; 31(1): 83-88.

[127] Sandritter TL, Kraus DM. Respiratory syncytial virus-immunoglobulin intravenous (RSV-IGIV) for respiratory syncytial viral infections: part I. J Pediatr Health Care. 1997; 11(6): 284-291. quiz 292–3.

[128] Robinson RF, Nahata MC. Respiratory syncytial virus (RSV) immune globulin and palivizumab for prevention of RSV infection. Am J Health Syst Pharm. 2000; 57(3): 259-264.

[129] McLellan JS. Neutralizing epitopes on the respiratory syncytial virus fusion glycoprotein. Curr Opin Virol. 2015; 11: 70-75.

[130] Melero JA, Mas V, McLellan JS. Structural, antigenic and immunogenic features of respiratory syncytial virus glycoproteins relevant for vaccine development. Vaccine. 2017; 35(3): 461-468.

[131] Ye X, Iwuchukwu OP, Avadhanula V, et al. Antigenic site-specific competitive antibody responses to the fusion protein of respiratory syncytial virus were associated with viral clearance in hematopoietic cell transplantation adults. Front Immunol. 2019; 10: 706.

[132] Cingoz O. Motavizumab. MAbs. 2009; 1(5): 439-442.

[133] Taleb SA, Al Thani AA, Al Ansari K, Yassine HM. Human respiratory syncytial virus: pathogenesis, immune responses, and current vaccine approaches. Eur J Clin Microbiol Infect Dis. 2018; 37(10): 1817-1827.

[134] Corti D, Bianchi S, Vanzetta F, et al. Cross-neutralization of four paramyxoviruses by a human monoclonal antibody. Nature. 2013; 501(7467): 439-443.

[135] McLellan JS, Chen M, Chang JS, et al. Structure of a major antigenic site on the respiratory syncytial virus fusion glycoprotein in complex with neutralizing antibody 101F. J Virol. 2010; 84(23): 12236-12244.

[136] Steward MW. The development of a mimotope-based synthetic peptide vaccine against respiratory syncytial virus. Biologicals. 2001; 29(3-4): 215-219.

[137] Tang A, Chen Z, Cox KS, et al. A potent broadly neutralizing human RSV antibody targets conserved site IV of the fusion glycoprotein. Nat Commun. 2019; 10(1): 4153.

[138] Zhao M, Zheng ZZ, Chen M, et al. Discovery of a prefusion respiratory syncytial virus F-specific monoclonal antibody that provides greater in vivo protection than the murine precursor of palivizumab. J Virol. 2017; 91(15): e00176-17.

[139] Sparrow E, Adetifa I, Chaiyakunapruk N, et al. WHO preferred product characteristics for monoclonal antibodies for passive immunization against respiratory syncytial virus (RSV) disease in infants—Key considerations for global use. Vaccine. 2022; 40(26): 3506-3510.

[140] Pollack P, Groothuis JR. Development and use of palivizumab (Synagis): a passive immunoprophylactic agent for RSV. J Infect Chemother. 2002; 8(3): 201-206.

[141] Scott LJ, Lamb HM. Palivizumab. Drugs. 1999; 58(2): 305-311. discussion 312–3.

[142] Narayan O, Bentley A, Mowbray K, et al. Updated cost-effectiveness analysis of palivizumab (Synagis) for the prophylaxis of respiratory syncytial virus in infant populations in the UK. J Med Econ. 2020; 23(12): 1640-1652.

[143] Caserta MT, O’Leary ST, Munoz FM, Ralston SL. Palivizumab prophylaxis in infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2023; 152(1): e2023061803. Committee On Infectious D.

[144] Jorgensen SCJ. Nirsevimab: review of pharmacology, antiviral activity and emerging clinical experience for respiratory syncytial virus infection in infants. J Antimicrob Chemother. 2023; 78(5): 1143-1149.

[145] Ahani B, Tuffy KM, Aksyuk AA, et al. Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials. Nat Commun. 2023; 14(1): 4347.

[146] Mankad VS, Leach A, Chang Y, et al. Comprehensive summary of safety data on nirsevimab in infants and children from all pivotal randomized clinical trials. Pathogens. 2024; 13(6): 503.

[147] Griffin MP, Yuan Y, Takas T, et al. Single-dose nirsevimab for prevention of RSV in preterm infants. N Engl J Med. 2020; 383(5): 415-425.

[148] Paireau J, Durand C, Raimbault S, et al. Nirsevimab effectiveness against cases of respiratory syncytial virus bronchiolitis hospitalised in paediatric intensive care units in france, september 2023-January 2024. Influenza Other Respir Viruses. 2024; 18(6): e13311.

[149] Ares-Gomez S, Mallah N, Santiago-Perez MI, et al. Effectiveness and impact of universal prophylaxis with nirsevimab in infants against hospitalisation for respiratory syncytial virus in Galicia, Spain: initial results of a population-based longitudinal study. Lancet Infect Dis. 2024; 24(8): 817-828.

[150] Lopez-Lacort M, Munoz-Quiles C, Mira-Iglesias A, et al. Early estimates of nirsevimab immunoprophylaxis effectiveness against hospital admission for respiratory syncytial virus lower respiratory tract infections in infants, Spain, October 2023 to January 2024. Euro Surveill. 2024; 29(6): 2400046.

[151] Moline HL, Tannis A, Toepfer AP, et al. Early estimate of nirsevimab effectiveness for prevention of respiratory syncytial virus-associated hospitalization among infants entering their first respiratory syncytial virus season—new vaccine surveillance network, October 2023-February 2024. MMWR Morb Mortal Wkly Rep. 2024; 73(9): 209-214.

[152] Fly JH, Eiland LS, Stultz JS. Nirsevimab: expansion of respiratory syncytial virus prevention options in neonates, infants, and at-risk young children. Ann Pharmacother. 2024:10600280241243357.

[153] Phuah JY, Maas BM, Tang A, et al. Quantification of clesrovimab, an investigational, half-life extended, anti-respiratory syncytial virus protein F human monoclonal antibody in the nasal epithelial lining fluid of healthy adults. Biomed Pharmacother. 2023; 169: 115851.

[154] Aliprantis AO, Wolford D, Caro L, et al. A phase 1 randomized, double-blind, placebo-controlled trial to assess the safety, tolerability, and pharmacokinetics of a respiratory syncytial virus neutralizing monoclonal antibody MK-1654 in healthy adults. Clin Pharmacol Drug Dev. 2021; 10(5): 556-566.

[155] Orito Y, Otani N, Matsumoto Y, et al. A phase I study to evaluate safety, pharmacokinetics, and pharmacodynamics of respiratory syncytial virus neutralizing monoclonal antibody MK-1654 in healthy Japanese adults. Clin Transl Sci. 2022; 15(7): 1753-1763.

[156] Yu JM, Fu YH, Peng XL, Zheng YP, He JS. Genetic diversity and molecular evolution of human respiratory syncytial virus A and B. Sci Rep. 2021; 11(1): 12941.

[157] Langedijk AC, Vrancken B, Lebbink RJ, et al. The genomic evolutionary dynamics and global circulation patterns of respiratory syncytial virus. Nat Commun. 2024; 15(1): 3083.

[158] Pinana M, Gonzalez-Sanchez A, Andres C, et al. Genomic evolution of human respiratory syncytial virus during a decade (2013-2023): bridging the path to monoclonal antibody surveillance. J Infect. 2024; 88(5): 106153.

[159] Langedijk AC, Harding ER, Konya B, et al. A systematic review on global RSV genetic data: identification of knowledge gaps. Rev Med Virol. 2022; 32(3): e2284.

[160] Shishir TA, Saha O, Rajia S, et al. Genome-wide study of globally distributed respiratory syncytial virus (RSV) strains implicates diversification utilizing phylodynamics and mutational analysis. Sci Rep. 2023; 13(1): 13531.

[161] Goya S, Ruis C, Neher RA, et al. Standardized phylogenetic classification of human respiratory syncytial virus below the subgroup level. Emerg Infect Dis. 2024; 30(8): 1631-1641.

[162] Langedijk AC, Lebbink RJ, Naaktgeboren C, et al. Global molecular diversity of RSV—the “INFORM RSV” study. BMC Infect Dis. 2020; 20(1): 450.

[163] DeVincenzo JP, Hall CB, Kimberlin DW, et al. Surveillance of clinical isolates of respiratory syncytial virus for palivizumab (Synagis)-resistant mutants. J Infect Dis. 2004; 190(5): 975-978.

[164] Jo WK, Schadenhofer A, Habierski A, et al. Reverse genetics systems for contemporary isolates of respiratory syncytial virus enable rapid evaluation of antibody escape mutants. Proc Natl Acad Sci U S A. 2021; 118(14): e2026558118.

[165] Simoes EAF, Forleo-Neto E, Geba GP, et al. Suptavumab for the prevention of medically attended respiratory syncytial virus infection in preterm infants. Clin Infect Dis. 2021; 73(11): e4400-e4408.

[166] Wilkins D, Langedijk AC, Lebbink RJ, et al. 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. 2023; 23(7): 856-866.

[167] Lin GL, Drysdale SB, Snape MD, et al. Distinct patterns of within-host virus populations between two subgroups of human respiratory syncytial virus. Nat Commun. 2021; 12(1): 5125.

[168] Sun M, Lai H, Na F, et al. Monoclonal antibody for the prevention of respiratory syncytial virus in infants and children: a systematic review and network meta-analysis. JAMA Netw Open. 2023; 6(2): e230023.

[169] Saez-Llorens X, Moreno MT, Ramilo O, et al. Safety and pharmacokinetics of palivizumab therapy in children hospitalized with respiratory syncytial virus infection. Pediatr Infect Dis J. 2004; 23(8): 707-712.

[170] Ramilo O, Lagos R, Saez-Llorens X, et al. Motavizumab treatment of infants hospitalized with respiratory syncytial virus infection does not decrease viral load or severity of illness. Pediatr Infect Dis J. 2014; 33(7): 703-709.

[171] Cunningham S, Piedra PA, Martinon-Torres F, et al. Nebulised ALX-0171 for respiratory syncytial virus lower respiratory tract infection in hospitalised children: a double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Respir Med. 2021; 9(1): 21-32.

[172] Van Heeke G, Allosery K, De Brabandere V, De Smedt T, Detalle L, de Fougerolles A. Nanobodies(R) as inhaled biotherapeutics for lung diseases. Pharmacol Ther. 2017; 169: 47-56.

[173] Oti VB, Idris A, McMillan NAJ. Intranasal antivirals against respiratory syncytial virus: the current therapeutic development landscape. Expert Rev Anti Infect Ther. 2024: 1-11.

[174] Makari D, Jensen KM, Harris B, Jafri HS. Randomized, double-blind study of the safety of the liquid versus lyophilized formulation of palivizumab in premature infants and children with chronic lung disease of prematurity. Infect Dis Ther. 2014; 3(2): 339-347.

[175] Carbonell-Estrany X, Simoes EA, Dagan R, et al. Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: a noninferiority trial. Pediatrics. 2010; 125(1): e35-51.

[176] Robbie GJ, Criste R, Dall’acqua WF, et al. A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults. Antimicrob Agents Chemother. 2013; 57(12): 6147-6153.

[177] Fernandez P, Trenholme A, Abarca K, et al. A phase 2, randomized, double-blind safety and pharmacokinetic assessment of respiratory syncytial virus (RSV) prophylaxis with motavizumab and palivizumab administered in the same season. BMC Pediatr. 2010; 10: 38.

[178] Esposito S, Abu-Raya B, Bonanni P, et al. Coadministration of anti-viral monoclonal antibodies with routine pediatric vaccines and implications for nirsevimab use: a white paper. Front Immunol. 2021; 12: 708939.

[179] Scotta MC, Stein RT. Current strategies and perspectives for active and passive immunization against Respiratory Syncytial Virus in childhood. J Pediatr (Rio J). 2023; 99: S4-S11. Suppl 1. Suppl 1.

[180] Shoukat A, Abdollahi E, Galvani AP, Halperin SA, Langley JM, Moghadas SM. Cost-effectiveness analysis of nirsevimab and maternal RSVpreF vaccine strategies for prevention of respiratory syncytial virus disease among infants in Canada: a simulation study. Lancet Reg Health Am. 2023; 28: 100629.

[181] Lopez-Lacort M, Corberan-Vallet A, Santonja FJ, Munoz-Quiles C, Diez-Domingo J, Orrico-Sanchez A. Potential impact of nirsevimab and bivalent maternal vaccine against RSV bronchiolitis in infants: a population-based modelling study. J Infect Public Health. 2024; 17(8): 102492.

[182] Ananworanich J, Heaton PM. Bringing preventive RSV monoclonal antibodies to infants in low-and middle-income countries: challenges and opportunities. Vaccines (Basel). 2021; 9(9): 961.

[183] Sun BW, Zhang PP, Wang ZH, et al. Prevention and potential treatment strategies for respiratory syncytial virus. Molecules. 2024; 29(3): 598.

[184] Xing Y, Proesmans M. New therapies for acute RSV infections: where are we?. Eur J Pediatr. 2019; 178(2): 131-138.

[185] Domachowske JB, Anderson EJ, Goldstein M. The future of respiratory syncytial virus disease prevention and treatment. Infect Dis Ther. 2021; 10: 47-60. Suppl 1.

[186] Bonneux B, Jacoby E, Ceconi M, Stobbelaar K, Delputte P, Herschke F. Direct-acting antivirals for RSV treatment, a review. Antiviral Res; 229:105948.

[187] Rosenberg HF, Domachowske JB. Inflammatory responses to respiratory syncytial virus (RSV) infection and the development of immunomodulatory pharmacotherapeutics. Curr Med Chem. 2012; 19(10): 1424-1431.

[188] Trang TP, Whalen M, Hilts-Horeczko A, Doernberg SB, Liu C. Comparative effectiveness of aerosolized versus oral ribavirin for the treatment of respiratory syncytial virus infections: a single-center retrospective cohort study and review of the literature. Transpl Infect Dis. 2018; 20(2): e12844.

[189] Wongsurakiat P, Sunhapanit S, Muangman N. Respiratory syncytial virus-associated acute respiratory illness in adult non-immunocompromised patients: outcomes, determinants of outcomes, and the effect of oral ribavirin treatment. Influenza Other Respir Viruses. 2022; 16(4): 767-779.

[190] Mir WAY, Shrestha DB, Rana W, Yelma Reddy SR, Paudel A, Verda L. Successful treatment of respiratory syncytial virus infection in an immunocompromised patient with ribavirin. Cureus. 2021; 13(8): e16930.

[191] Nilsson AC, Pullman J, Napora P, et al. A pilot phase 2a, randomized, double-blind, placebo-controlled study to explore the antiviral activity, clinical outcomes, safety, and tolerability of rilematovir at two dose levels in non-hospitalized adults with respiratory syncytial virus infection. Clin Microbiol Infect. 2023; 29(10): 1320-1327.

[192] Ferrero F, Lin CY, Liese J, et al. CROCuS, a phase II study evaluating the antiviral activity, clinical outcomes, and safety of rilematovir in children aged >/= 28 days and </= 3 years with acute respiratory tract infection due to respiratory syncytial virus. Paediatr Drugs. 2024; 26(4): 411-427.

[193] Huang LM, Schibler A, Huang YC, et al. Safety and efficacy of AK0529 in respiratory syncytial virus-infected infant patients: a phase 2 proof-of-concept trial. Influenza Other Respir Viruses. 2023; 17(7): e13176.

[194] DeVincenzo JP, Whitley RJ, Mackman RL, et al. Oral GS-5806 activity in a respiratory syncytial virus challenge study. N Engl J Med. 2014; 371(8): 711-722.

[195] Marty FM, Chemaly RF, Mullane KM, et al. A phase 2b, randomized, double-blind, placebo-controlled multicenter study evaluating antiviral effects, pharmacokinetics, safety, and tolerability of presatovir in hematopoietic cell transplant recipients with respiratory syncytial virus infection of the lower respiratory tract. Clin Infect Dis. 2020; 71(11): 2787-2795.

[196] Chemaly RF, Dadwal SS, Bergeron A, et al. A phase 2, randomized, double-blind, placebo-controlled trial of presatovir for the treatment of respiratory syncytial virus upper respiratory tract infection in hematopoietic-cell transplant recipients. Clin Infect Dis. 2020; 71(11): 2777-2786.

[197] Gottlieb J, Torres F, Haddad T, et al. A randomized controlled trial of presatovir for respiratory syncytial virus after lung transplant. J Heart Lung Transplant. 2023; 42(7): 908-916.

[198] Cockerill GS, Angell RM, Bedernjak A, et al. Discovery of sisunatovir (RV521), an inhibitor of respiratory syncytial virus fusion. J Med Chem. 2021; 64(7): 3658-3676.

[199] DeVincenzo J, Tait D, Efthimiou J, et al. 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. 2020; 64(2): e01884-19.

[200] Coates M, Brookes D, Kim YI, et al. Preclinical characterization of PC786, an inhaled small-molecule respiratory syncytial virus l protein polymerase inhibitor. Antimicrob Agents Chemother. 2017; 61(9): e00737-17.

[201] Brookes DW, Coates M, Allen H, et al. 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. 2018; 175(12): 2520-2534.

[202] DeVincenzo J, Cass L, Murray A, et al. Safety and antiviral effects of nebulized PC786 in a respiratory syncytial virus challenge study. J Infect Dis. 2022; 225(12): 2087-2096.

[203] DeVincenzo JP, McClure MW, Symons JA, et al. Activity of oral ALS-008176 in a respiratory syncytial virus challenge study. N Engl J Med. 2015; 373(21): 2048-2058.

[204] Patel K, Kirkpatrick CM, Nieforth KA, et al. Respiratory syncytial virus-A dynamics and the effects of lumicitabine, a nucleoside viral replication inhibitor, in experimentally infected humans. J Antimicrob Chemother. 2019; 74(2): 442-452.

[205] Oey A, McClure M, Symons JA, et al. an orally administered nucleoside analog, in infants hospitalized with respiratory syncytial virus (RSV) infection: safety, efficacy, and pharmacokinetic results. PLoS One. 2023; 18(7): e0288271.

[206] Chapman J, Abbott E, Alber DG, et al. RSV604, a novel inhibitor of respiratory syncytial virus replication. Antimicrob Agents Chemother. 2007; 51(9): 3346-3353.

[207] DeVincenzo J, Cehelsky JE, Alvarez R, et al. Evaluation of the safety, tolerability and pharmacokinetics of ALN-RSV01, a novel RNAi antiviral therapeutic directed against respiratory syncytial virus (RSV). Antiviral Res. 2008; 77(3): 225-231.

[208] Boukhvalova MS, Prince GA, Blanco JC. Inactivation of respiratory syncytial virus by zinc finger reactive compounds. Virol J. 2010; 7: 20.

[209] Laganas VA, Dunn EF, McLaughlin RE, et al. Characterization of novel respiratory syncytial virus inhibitors identified by high throughput screen. Antiviral Res. 2015; 115: 71-74.

[210] Hara K, Yaita K, Khamrin P, et al. A small fragmented P protein of respiratory syncytial virus inhibits virus infection by targeting P protein. J Gen Virol. 2020; 101(1): 21-32.

[211] Li J, Xue L, Wang J, et al. Activation of the chemokine receptor CCR1 and preferential recruitment of galphai suppress RSV replication: implications for developing novel respiratory syncytial virus treatment strategies. J Virol. 2022; 96(22): e0130922.

[212] Shirato K, Ujike M, Kawase M, Matsuyama S. Identification of CCL2, RARRES2 and EFNB2 as host cell factors that influence the multistep replication of respiratory syncytial virus. Virus Res. 2015; 210: 213-226.

[213] Huynh H, Levitz R, Huang R, Kahn JS. mTOR kinase is a therapeutic target for respiratory syncytial virus and coronaviruses. Sci Rep. 2021; 11(1): 24442.

[214] Jorquera PA, Mathew C, Pickens J, et al. Verdinexor (KPT-335), a selective inhibitor of nuclear export, reduces respiratory syncytial virus replication in vitro. J Virol. 2019; 93(4): e01684-18.

[215] Mastrangelo P, Norris MJ, Duan W, Barrett EG, Moraes TJ, Hegele RG. Targeting host cell surface nucleolin for RSV therapy: challenges and opportunities. Vaccines (Basel). 2017; 5(3): 27.

[216] Perron M, Stray K, Kinkade A, et al. GS-5806 inhibits a broad range of respiratory syncytial virus clinical isolates by blocking the virus-cell fusion process. Antimicrob Agents Chemother. 2015; 60(3): 1264-1273.

[217] Stray K, Perron M, Porter DP, et al. Drug resistance assessment following administration of respiratory syncytial virus (RSV) fusion inhibitor presatovir to participants experimentally infected with RSV. J Infect Dis. 2020; 222(9): 1468-1477.

[218] Porter DP, Guo Y, Perry J, et al. Assessment of drug resistance during phase 2b clinical trials of presatovir in adults naturally infected with respiratory syncytial virus. Antimicrob Agents Chemother. 2020; 64(9): e02312-19.

[219] Gao Y, Cao J, Xing P, Altmeyer R, Zhang Y. Evaluation of small molecule combinations against respiratory syncytial virus in vitro. Molecules. 2021; 26(9): 2607.

[220] Ye Q, Wang D. Epidemiological changes of common respiratory viruses in children during the COVID-19 pandemic. J Med Virol. 2022; 94(5): 1990-1997.

[221] Abu-Raya B, Vineta Paramo M, Reicherz F, Lavoie PM. Why has the epidemiology of RSV changed during the COVID-19 pandemic? EClinicalMedicine. 2023; 61: 102089.

[222] Mathew S, Taleb S, Eid AH, Althani AA, Yassine HM. In silico virtual screening of lead compounds for major antigenic sites in respiratory syncytial virus fusion protein. Emergent Mater. 2022; 5(2): 295-305.

RIGHTS & PERMISSIONS

2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.