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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| Vydáno v: | International journal of molecular sciences Ročník 24; číslo 16; s. 12933 |
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01.08.2023
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| ISSN: | 1422-0067, 1661-6596, 1422-0067 |
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| Abstract | 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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| AbstractList | 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. 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.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. |
| Audience | Academic |
| Author | Galochkina, Anastasia V. Shtro, Anna A. Nikolaeva, Yulia V. Lozhkov, Aleksey A. Bobkov, Danila E. Salakhutdinov, Nariman F. Sivak, Konstantin V. Garshinina, Anzhelika V. Khomenko, Tatyana M. Volcho, Konstantin P. Klabukov, Artem M. Komissarov, Andrey B. Yakovlev, Kirill S. Borisevich, Sophia S. |
| AuthorAffiliation | 2 Vorozhtsov Novosibirsk Institute of Organic Chemistry, Acad. Lavrentyev av. 9, 630090 Novosibirsk, Russia; chomenko@nioch.nsc.ru (T.M.K.); volcho@nioch.nsc.ru (K.P.V.); anvar@nioch.nsc.ru (N.F.S.) 1 Smorodintsev Research Institute of Influenza, Professora Popova str, 15/17, 197376 St. Petersburg, Russia; temaklab@gmail.com (A.M.K.); garshininaang@gmail.com (A.V.G.); nastyagalochkina@gmail.com (A.V.G.); ulechka.s89@gmail.com (Y.V.N.); bobkovde@yandex.ru (D.E.B.); aswert6@mail.ru (A.A.L.); kvsivak@gmail.com (K.V.S.); kirikus-fly@yandex.ru (K.S.Y.); abkomissarov@gmail.com (A.B.K.) 3 Institute of Cytology Russian Academy of Science, Tikhoretsky av., 4, 194064 St. Petersburg, Russia 4 Ufa Chemistry Institute of the Ufa Federal Research Center, 71 Octyabrya pr., 450054 Ufa, Russia; monrel@mail.ru |
| AuthorAffiliation_xml | – name: 3 Institute of Cytology Russian Academy of Science, Tikhoretsky av., 4, 194064 St. Petersburg, Russia – name: 1 Smorodintsev Research Institute of Influenza, Professora Popova str, 15/17, 197376 St. Petersburg, Russia; temaklab@gmail.com (A.M.K.); garshininaang@gmail.com (A.V.G.); nastyagalochkina@gmail.com (A.V.G.); ulechka.s89@gmail.com (Y.V.N.); bobkovde@yandex.ru (D.E.B.); aswert6@mail.ru (A.A.L.); kvsivak@gmail.com (K.V.S.); kirikus-fly@yandex.ru (K.S.Y.); abkomissarov@gmail.com (A.B.K.) – name: 2 Vorozhtsov Novosibirsk Institute of Organic Chemistry, Acad. Lavrentyev av. 9, 630090 Novosibirsk, Russia; chomenko@nioch.nsc.ru (T.M.K.); volcho@nioch.nsc.ru (K.P.V.); anvar@nioch.nsc.ru (N.F.S.) – name: 4 Ufa Chemistry Institute of the Ufa Federal Research Center, 71 Octyabrya pr., 450054 Ufa, Russia; monrel@mail.ru |
| Author_xml | – sequence: 1 givenname: Anna A. surname: Shtro fullname: Shtro, Anna A. – sequence: 2 givenname: Artem M. orcidid: 0000-0002-7922-508X surname: Klabukov fullname: Klabukov, Artem M. – sequence: 3 givenname: Anzhelika V. surname: Garshinina fullname: Garshinina, Anzhelika V. – sequence: 4 givenname: Anastasia V. surname: Galochkina fullname: Galochkina, Anastasia V. – sequence: 5 givenname: Yulia V. surname: Nikolaeva fullname: Nikolaeva, Yulia V. – sequence: 6 givenname: Tatyana M. surname: Khomenko fullname: Khomenko, Tatyana M. – sequence: 7 givenname: Danila E. surname: Bobkov fullname: Bobkov, Danila E. – sequence: 8 givenname: Aleksey A. orcidid: 0000-0001-5906-7136 surname: Lozhkov fullname: Lozhkov, Aleksey A. – sequence: 9 givenname: Konstantin V. orcidid: 0000-0003-4064-5033 surname: Sivak fullname: Sivak, Konstantin V. – sequence: 10 givenname: Kirill S. orcidid: 0000-0001-7000-3467 surname: Yakovlev fullname: Yakovlev, Kirill S. – sequence: 11 givenname: Andrey B. surname: Komissarov fullname: Komissarov, Andrey B. – sequence: 12 givenname: Sophia S. orcidid: 0000-0001-8481-0470 surname: Borisevich fullname: Borisevich, Sophia S. – sequence: 13 givenname: Konstantin P. orcidid: 0000-0002-4083-9324 surname: Volcho fullname: Volcho, Konstantin P. – sequence: 14 givenname: Nariman F. surname: Salakhutdinov fullname: Salakhutdinov, Nariman F. |
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| Cites_doi | 10.3390/molecules26092607 10.1038/nchembio.1982 10.3390/molecules28062673 10.1093/oxfordjournals.jbchem.a022639 10.3390/ph15091158 10.1371/journal.pone.0126959 10.3390/molecules26247493 10.1016/S0140-6736(10)60206-1 10.1073/pnas.85.3.900 10.1021/acs.jmedchem.0c00226 |
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| SubjectTerms | Analysis Antibodies Antigens Antiviral drugs Cell culture Drug dosages Epidemics Health aspects Immunization Infection Infections Lung diseases Lungs Microscopy Newborn babies Palivizumab Pharmacokinetics Respiratory syncytial virus Russia |
| Title | Identification and Study of the Action Mechanism of Small Compound That Inhibits Replication of Respiratory Syncytial Virus |
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