A synthetic peptide mimicking the antigenic site of F protein suppresses of respiratory syncytial virus infection in vitro
AbstractIntroduction. Respiratory syncytial virus (RSV) is one of the most common pathogens causing respiratory diseases. There are no effective vaccines against RSV infection. At the same time, the use of monoclonal antibodies for immunoprophylaxis is limited by its high cost. Ribavirin is used for pharmacotherapy, but it causes numerous side effects. One of the most promising approaches is the use of natural and synthetic peptides as antivirals. Detailed studies of virion structure identified leading role of viral glycoprotein F in initiation of the infection. Molecular and immunological mapping of the F protein revealed the functional HR-1 and HR-2 domains. The flexibility of these domains provides the fusion of the virion with the cell. At the same time, inside HR-1 domain was identified so-called zero antigenic site Ø. Inactivation of this site significantly inhibits the infectious process.
The aim of the study was to design a peptide that mimics the antigenic site Ø of the F protein and its branched analog and study the antiviral properties of these peptides against RSV.
Material and methods. The peptides were synthesized by the solid phase method, and the high-performance liquid chromatography was used for purification. Authenticity was confirmed by mass spectrometry. Cytotoxicity was studied in the MTT test. Antiviral activity was studied in in vitro experiments using MA-104 cell culture, which in sensitive to RSV. The ELISA was used to study the ability of peptides to interact with RSV and with the cell receptor.
Results. Linear peptide KK-44 interacted with the virus, but had no significant effect on the infectious process. At the same time, the branched analog (KK-45 peptide) significantly inhibited RSV infection in vitro using several possible mechanisms: 1) by interacting with the F fusion protein, preventing its functioning; 2) by competitive inhibition of the receptor – nucleolin protein.
Conclusion. The branched peptide KK-45 possesses antiviral properties against RSV, which makes it promising for possible therapeutic applications.
Keywords:RSV infection; antiviral peptides; antigenic site Ø; laboratory animals
For citation: Shilovskiy I.P., Yumashev K.V., Kozhikhova K.V., Vishnyakova L.I., Smirnov V.V., Gudima G.O., Brylina V.E., Kaganova M.M., Nikolskii A.A., Timotievich E.D., Kovchina V.I., Rusak T.E., Shatilova A.V., Shatilov A.A., Andreev S.M., Kudlay D.A., Khaitov M.R. A synthetic peptide mimicking the antigenic site of F protein suppresses of respiratory syncytial virus infection in vitro. Immunologiya. 2023; 44 (2): 134–46. DOI: https://doi.org/10.33029/0206-4952-2023-44-2-134-146 (in Russian)
Funding. The study was supported by Russian Science Foundation grant No. 22-25-00182, https://rscf.ru/project/22-25-00182/.
Conflict of interests. The authors declare no conflict of interests.
Authors’ contribution. Study conception and design – Shilovskiy I.P., Khaitov M.R.; material collection and processing – Timotievich E.D., Nikolskii A.A., Kozhikhova K.V., Kovchina V.I., Vishnyakova L.I., Yumashev K.V., Kaganova M.M., Rusak T.E., Shatilov A.A., Shatilova A.V.; statistical processing – Andreev S.M., Shilovskiy I.P.; article preparation – Shilovskiy I.P., Yumashev K.V.; editing – Gudima G.O., Kudlay D.A., Smirnov V.V., Andreev S.M., Brylina V.E.
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