General Information of Drug Therapeutic Target (DTT) (ID: TT57ID8)

DTT Name Respiratory syncytial virus protein F (RSV F)
Synonyms Protein F; Fusion glycoprotein F1; Fusion glycoprotein F0; F
Gene Name RSV F
DTT Type
Successful target
[1]
UniProt ID
FUS_HRSVA
TTD ID
T07485
Sequence
MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIE
LSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPPTNNRARRELPRFMNYTLN
NAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVS
LSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSISNIETVIEFQQKNNRLLEITREFSVN
AGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYV
VQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKV
QSNRVFCDTMNSLTLPSEINLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKT
KCTASNKNRGIIKTFSNGCDYVSNKGMDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDP
LVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIVILLS
LIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN
Function
Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion, the heptad repeat (HR) regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C- terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and plasma cell membranes. Directs fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs directly at the outer cell membrane. The trimer of F1-F2 (protein F) interacts with glycoprotein G at the virion surface. Upon binding of G to heparan sulfate, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between host cell and virion membranes. Notably, RSV fusion protein is able to interact directly with heparan sulfate and therefore actively participates in virus attachment. Furthermore, the F2 subunit was identifed as the major determinant of RSV host cell specificity. Later in infection, proteins F expressed at the plasma membrane of infected cells mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis. The fusion protein is also able to trigger p53- dependent apoptosis.

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
2 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Lasofoxifene DMHA18P Osteoporosis FB83.0 Approved [2]
Palivizumab DMQM9S0 Respiratory syncytial virus infection 1C80 Approved [1]
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7 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Motavizumab DMB24H7 Respiratory syncytial virus infection 1C80 Phase 3 [3]
SAR438584 DMDMAE4 Respiratory syncytial virus infection 1C80 Phase 3 [4]
MK-1654 DM2YNMI Respiratory syncytial virus infection 1C80 Phase 2/3 [5]
GS-5806 DMDAHL6 Respiratory syncytial virus infection 1C80 Phase 2 [6]
JNJ-53718678 DMJ1FXL Respiratory syncytial virus infection 1C80 Phase 2 [7]
RV521 DMSW5XJ Respiratory syncytial virus infection 1C80 Phase 2 [8]
MEDI-557 DM6ADMG Respiratory syncytial virus infection 1C80 Phase 1 [3]
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⏷ Show the Full List of 7 Clinical Trial Drug(s)
1 Preclinical Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
TMC-353121 DMDSJO8 Respiratory syncytial virus infection 1C80 Preclinical [2]
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1 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
CL-387626 DMA4DNX Virus infection 1A24-1D9Z Terminated [9]
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References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
2 Prospects for the development of fusion inhibitors to treat human respiratory syncytial virus infection. Curr Opin Drug Discov Devel. 2009 Jul;12(4):479-87.
3 Motavizumab. Correction in: MAbs. 2010 Sep-Oct; 2(5): 591.
4 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800040470)
5 A potent broadly neutralizing human RSV antibody targets conserved site IV of the fusion glycoprotein. Nat Commun. 2019 Sep 12;10(1):4153.
6 Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806) and clinical proof of concept in a human RSV challenge study. J Med Chem. 2015 Feb 26;58(4):1630-43.
7 Antiviral Activity of Oral JNJ-53718678 in Healthy Adult Volunteers Challenged With Respiratory Syncytial Virus: A Placebo-Controlled Study. J Infect Dis. 2018 Jul 24;218(5):748-756.
8 Discovery of Sisunatovir (RV521), an Inhibitor of Respiratory Syncytial Virus Fusion. J Med Chem. 2021 Apr 8;64(7):3658-3676.
9 Respiratory Syncytial Virus Entry Inhibitors Targeting the F Protein. Viruses. 2013 January; 5(1): 211-225.