F inhibitors bind F on RSV virion

Stable Identifier
R-HSA-9845143
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Human respiratory syncytial virus A
Compartment
extracellular region
ReviewStatus
5/5
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F inhibitors bind F on RSV virion
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Several F inhibitors bind the hRSV A fusion (F) protein on the virion and prevent F from initiating viral fusion with the cell membrane, abolishing viral entry. The monoclonal antibody palivizumab was approved in 1998 and is recommended as prophylactic treatment for infants at high risk for RSV due to conditions such as prematurity or other medical problems, including heart or lung diseases. It is administered once per month during the RSV high-risk season (September to November) and reduces the risk of infection by half, having minor side effects (reviewed by Wang et al., 2011). Nirsevimab is the second monoclonal antibody for preventing respiratory syncytial virus lower respiratory tract disease. It was approved in 2023 for prophylaxis in neonates and infants during their first RSV season. It is administered as a 1-dose intramuscular injection shortly before or during the RSV season since it has an extended half-life (Jones et al., 2023). However, the CDC recommends nirsevimab as prophylaxis for older people with increased risk (CDC, 2023). The nanobody ALX-0171 (Gontivimab) was designed as an inhalation to target the F protein. It showed antiviral effects in hospitalized RSV-Infected infants but no consistent differences in clinical outcome measures (NCT02979431); a second trial was terminated early because of the lack of clinical efficacy (NCT03418571). Further development of ALX-0171 was stopped by the producing company (Lowensteyn & Bont, 2020). The small molecule F inhibitor rilematovir showed a reduction of time to resolution of key RSV symptoms in a phase 2b trial (Nilsson et al., 2023). Sisunatovir (RV521) is a small molecule investigated in two phase 2 trials and showed safety and efficacy (NCT04267822, NCT04225897). However, the producing company withdrew the product due to strategic considerations (Cockerill et al., 2021). Ziresovir was safe and efficient in a phase 3 trial treating infants hospitalized with RSV (NCT04231968; Zheng et al., 2019; reviewed in Langedijk & Bond, 2021). China's National Medical Products Administration granted it priority review status in December 2022.
Literature References
PubMed ID Title Journal Year
31194544 Discovery of Ziresovir as a Potent, Selective, and Orally Bioavailable Respiratory Syncytial Virus Fusion Protein Inhibitor

Xiang, K, Zheng, X, Zhang, B, Gao, L, Yun, H, Shen, HC, Wang, L, Wang, B, Wu, JZ, Yu, X, Feng, S, Guo, T, Liang, C, Chen, L, Zhou, M, Liu, Y, Zou, G

J Med Chem 2019
37438492 Respiratory syncytial virus infection and novel interventions

Langedijk, AC, Bont, LJ

Nat Rev Microbiol 2023
37422079 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

Stevens, M, Draghi, J, Scott, J, Aggarwal, N, Napora, P, Rusch, S, Vijgen, L, Ianus, J, Pullman, J, Sinha, R, Petrova, G, Bertzos, K, Luz, K, Huntjens, D, Gupta, A, Guzman Romero, AK, Nilsson, AC

Clin Microbiol Infect 2023
31915814 Clinical Development of Respiratory Syncytial Virus Antivirals-What We Can Learn From Oseltamivir

Löwensteyn, YN, Bont, LJ

Clin Infect Dis 2020
37616235 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

Roper, LE, Mahon, BE, Sánchez, PJ, Long, SS, Kotton, CN, Meyer, S, Brooks, O, McMorrow, ML, Jones, JM, Prill, MM, Fleming-Dutra, KE

MMWR Morb Mortal Wkly Rep 2023
33729773 Discovery of Sisunatovir (RV521), an Inhibitor of Respiratory Syncytial Virus Fusion

Williams, G, Ludes-Meyers, JH, Mathews, N, Thom, M, Chuckowree, I, Bedernjak, A, Powell, K, Young, P, Fraser, I, Good, JAD, Tait, D, Watterson, D, McLellan, JS, Taylor, G, Littler, E, Thomas, E, Ward, SE, Gascon-Simorte, J, Lumley, J, Harland, R, Angell, RM, Villalonga Barber, C, Lunn, G, Johnson, SM, Scott, C, Paradowski, M, Peeples, ME, Cockerill, GS, Gilman, MSA

J Med Chem 2021
21281564 Palivizumab for immunoprophylaxis of respiratory syncytial virus (RSV) bronchiolitis in high-risk infants and young children: a systematic review and additional economic modelling of subgroup analyses

Meads, C, Wang, D, Bayliss, S

Health Technol Assess 2011
  CDC Recommends RSV Vaccine For Older Adults

Centers for Disease Control and Prevention USA, The

   
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Authored
Stephan, R  (2023-09-27)
Reviewed
Bergeron, HC  (2023-11-03)
Created
Stephan, R  (2023-09-27)
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