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Identification and Study of the Action Mechanism of Small Compound That Inhibits Replication of Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) is known to cause annual epidemics of respiratory infections; however, the lack of specific treatment options for this disease poses a challenge. In light of this, there has been a concerted effort to identify small molecules that can effectively combat RSV. This ar...

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Autores principales: Shtro, Anna A., Klabukov, Artem M., Garshinina, Anzhelika V., Galochkina, Anastasia V., Nikolaeva, Yulia V., Khomenko, Tatyana M., Bobkov, Danila E., Lozhkov, Aleksey A., Sivak, Konstantin V., Yakovlev, Kirill S., Komissarov, Andrey B., Borisevich, Sophia S., Volcho, Konstantin P., Salakhutdinov, Nariman F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454904/
https://www.ncbi.nlm.nih.gov/pubmed/37629115
http://dx.doi.org/10.3390/ijms241612933
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author Shtro, Anna A.
Klabukov, Artem M.
Garshinina, Anzhelika V.
Galochkina, Anastasia V.
Nikolaeva, Yulia V.
Khomenko, Tatyana M.
Bobkov, Danila E.
Lozhkov, Aleksey A.
Sivak, Konstantin V.
Yakovlev, Kirill S.
Komissarov, Andrey B.
Borisevich, Sophia S.
Volcho, Konstantin P.
Salakhutdinov, Nariman F.
author_facet Shtro, Anna A.
Klabukov, Artem M.
Garshinina, Anzhelika V.
Galochkina, Anastasia V.
Nikolaeva, Yulia V.
Khomenko, Tatyana M.
Bobkov, Danila E.
Lozhkov, Aleksey A.
Sivak, Konstantin V.
Yakovlev, Kirill S.
Komissarov, Andrey B.
Borisevich, Sophia S.
Volcho, Konstantin P.
Salakhutdinov, Nariman F.
author_sort Shtro, Anna A.
collection PubMed
description Respiratory syncytial virus (RSV) is known to cause annual epidemics of respiratory infections; however, the lack of specific treatment options for this disease poses a challenge. In light of this, there has been a concerted effort to identify small molecules that can effectively combat RSV. This article focuses on the mechanism of action of compound K142, which was identified as a primary screening leader in the earlier stages of the project. The research conducted demonstrates that K142 significantly reduces the intensity of virus penetration into the cells, as well as the formation of syncytia from infected cells. These findings show that the compound’s interaction with the surface proteins of RSV is a key factor in its antiviral activity. Furthermore, pharmacological modeling supports that K142 effectively interacts with the F-protein. However, in vivo studies have shown only weak antiviral activity against RSV infection, with a slight decrease in viral load observed in lung tissues. As a result, there is a need to enhance the bioavailability or antiviral properties of this compound. Based on these findings, we hypothesize that further modifications of the compound under study could potentially increase its antiviral activity.
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spelling pubmed-104549042023-08-26 Identification and Study of the Action Mechanism of Small Compound That Inhibits Replication of Respiratory Syncytial Virus Shtro, Anna A. Klabukov, Artem M. Garshinina, Anzhelika V. Galochkina, Anastasia V. Nikolaeva, Yulia V. Khomenko, Tatyana M. Bobkov, Danila E. Lozhkov, Aleksey A. Sivak, Konstantin V. Yakovlev, Kirill S. Komissarov, Andrey B. Borisevich, Sophia S. Volcho, Konstantin P. Salakhutdinov, Nariman F. Int J Mol Sci Article Respiratory syncytial virus (RSV) is known to cause annual epidemics of respiratory infections; however, the lack of specific treatment options for this disease poses a challenge. In light of this, there has been a concerted effort to identify small molecules that can effectively combat RSV. This article focuses on the mechanism of action of compound K142, which was identified as a primary screening leader in the earlier stages of the project. The research conducted demonstrates that K142 significantly reduces the intensity of virus penetration into the cells, as well as the formation of syncytia from infected cells. These findings show that the compound’s interaction with the surface proteins of RSV is a key factor in its antiviral activity. Furthermore, pharmacological modeling supports that K142 effectively interacts with the F-protein. However, in vivo studies have shown only weak antiviral activity against RSV infection, with a slight decrease in viral load observed in lung tissues. As a result, there is a need to enhance the bioavailability or antiviral properties of this compound. Based on these findings, we hypothesize that further modifications of the compound under study could potentially increase its antiviral activity. MDPI 2023-08-18 /pmc/articles/PMC10454904/ /pubmed/37629115 http://dx.doi.org/10.3390/ijms241612933 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shtro, Anna A.
Klabukov, Artem M.
Garshinina, Anzhelika V.
Galochkina, Anastasia V.
Nikolaeva, Yulia V.
Khomenko, Tatyana M.
Bobkov, Danila E.
Lozhkov, Aleksey A.
Sivak, Konstantin V.
Yakovlev, Kirill S.
Komissarov, Andrey B.
Borisevich, Sophia S.
Volcho, Konstantin P.
Salakhutdinov, Nariman F.
Identification and Study of the Action Mechanism of Small Compound That Inhibits Replication of Respiratory Syncytial Virus
title Identification and Study of the Action Mechanism of Small Compound That Inhibits Replication of Respiratory Syncytial Virus
title_full Identification and Study of the Action Mechanism of Small Compound That Inhibits Replication of Respiratory Syncytial Virus
title_fullStr Identification and Study of the Action Mechanism of Small Compound That Inhibits Replication of Respiratory Syncytial Virus
title_full_unstemmed Identification and Study of the Action Mechanism of Small Compound That Inhibits Replication of Respiratory Syncytial Virus
title_short Identification and Study of the Action Mechanism of Small Compound That Inhibits Replication of Respiratory Syncytial Virus
title_sort identification and study of the action mechanism of small compound that inhibits replication of respiratory syncytial virus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454904/
https://www.ncbi.nlm.nih.gov/pubmed/37629115
http://dx.doi.org/10.3390/ijms241612933
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