Target intelligence / Profile preview

Respiratory syncytial virus fusion glycoprotein, antigenic site IV (RSV F site IV)

Target
RSV F site IV
Molecular classification
Viral protein, Fusion protein, Epitope, Antigenic site
01

Overview

Antigenic site IV is a major neutralizing epitope located on the Respiratory Syncytial Virus (RSV) fusion (F) glycoprotein. It is a relatively conserved, linear epitope (residues 422-438) found in domain II of the F protein, and it remains accessible in both the pre-fusion and post-fusion conformations [1, 2, 5]. Antibodies targeting this site, such as the monoclonal antibody 101F and the clinical candidate clesrovimab (MK-1654), neutralize the virus by inhibiting the fusion of the viral envelope with the host cell membrane [2, 15, 21]. Because site IV is highly conserved across RSV subtypes (A and B) and even some other pneumoviruses like human metapneumovirus (hMPV), it is a key target for the development of broad-spectrum prophylactic and therapeutic agents [5, 22, 27]. Clesrovimab, a long-acting monoclonal antibody targeting this site, has shown significant efficacy in Phase 3 clinical trials for preventing RSV-associated lower respiratory tract disease in infants [15, 22].

Other names
Site IVSite CRSV F antigenic site IVRSV F site CAntigenic site IV of RSV F proteinRSHZ19 epitope
02

Mechanism of action

Neutralization of RSV by binding to the F protein and blocking the fusion of the viral envelope with the host cell membrane.

03

Biological functions

Viral entryMembrane fusionViral infectionViral neutralization
04

Disease associations

InfectionRespiratory syncytial virus infectionBronchiolitisPneumonia
05

Safety considerations

Viral escape mutationsAntibody resistanceLack of clinical efficacyHypersensitivity reactions
06

Interacting drugs

Clesrovimab

4 more in the full profile.

07

Biomarkers

RSV viral loadNeutralizing antibody titersRSV F protein expression

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