Can Modern Molecular Modeling Methods Help Find the Area of Potential Vulnerability of Flaviviruses?
Flaviviruses are single-stranded RNA viruses that have emerged in recent decades and infect up to 400 million people annually, causing a variety of potentially severe pathophysiological processes including hepatitis, encephalitis, hemorrhagic fever, tissues and capillaries damage. The <i>Flavi...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/14/7721 |
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| author | Daniil V. Shanshin Sophia S. Borisevich Alexander A. Bondar Yuri B. Porozov Elena A. Rukhlova Elena V. Protopopova Nikita D. Ushkalenko Valery B. Loktev Andrei I. Chapoval Alexander A. Ilyichev Dmitriy N. Shcherbakov |
| author_facet | Daniil V. Shanshin Sophia S. Borisevich Alexander A. Bondar Yuri B. Porozov Elena A. Rukhlova Elena V. Protopopova Nikita D. Ushkalenko Valery B. Loktev Andrei I. Chapoval Alexander A. Ilyichev Dmitriy N. Shcherbakov |
| author_sort | Daniil V. Shanshin |
| collection | DOAJ |
| description | Flaviviruses are single-stranded RNA viruses that have emerged in recent decades and infect up to 400 million people annually, causing a variety of potentially severe pathophysiological processes including hepatitis, encephalitis, hemorrhagic fever, tissues and capillaries damage. The <i>Flaviviridae</i> family is represented by four genera comprising 89 known virus species. There are no effective therapies available against many pathogenic flaviviruses. One of the promising strategies for flavivirus infections prevention and therapy is the use of neutralizing antibodies (NAb) that can disable the virus particles from infecting the host cells. The envelope protein (E protein) of flaviviruses is a three-domain structure that mediates the fusion of viral and host membranes delivering the infectious material. We previously developed and characterized 10H10 mAb which interacts with the E protein of the tick-borne encephalitis virus (TBEV) and many other flaviviruses’ E proteins. The aim of this work was to analyze the structure of E protein binding sites recognized by the 10H10 antibody, which is reactive with different flavivirus species. Here, we present experimental data and 3D modeling indicating that the 10H10 antibody recognizes the amino acid sequence between the two cysteines C92-C116 of the fusion loop (FL) region of flaviviruses’ E proteins. Overall, our results indicate that the antibody-antigen complex can form a rigid or dynamic structure that provides antibody cross reactivity and efficient interaction with the fusion loop of E protein. |
| first_indexed | 2024-03-09T13:42:04Z |
| format | Article |
| id | doaj.art-2d21298859e547d38d52c188b7d39a07 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:42:04Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2d21298859e547d38d52c188b7d39a072023-11-30T21:05:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012314772110.3390/ijms23147721Can Modern Molecular Modeling Methods Help Find the Area of Potential Vulnerability of Flaviviruses?Daniil V. Shanshin0Sophia S. Borisevich1Alexander A. Bondar2Yuri B. Porozov3Elena A. Rukhlova4Elena V. Protopopova5Nikita D. Ushkalenko6Valery B. Loktev7Andrei I. Chapoval8Alexander A. Ilyichev9Dmitriy N. Shcherbakov10State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, RussiaLaboratory of Physical Chemistry, Ufa Institute of Chemistry, Ufa Federal Research Center Russian Academy of Science, 450054 Ufa, RussiaInstitute of Chemical Biology and Fundamental Medicine, 630090 Novosibirsk, RussiaThe Center of Bio- and Chemoinformatics, I.M. Sechenov First Moscow State Medical University, 119435 Moscow, RussiaState Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, RussiaRussian-American Anti-Cancer Center, Altai State University, 656049 Barnaul, RussiaState Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, RussiaFlaviviruses are single-stranded RNA viruses that have emerged in recent decades and infect up to 400 million people annually, causing a variety of potentially severe pathophysiological processes including hepatitis, encephalitis, hemorrhagic fever, tissues and capillaries damage. The <i>Flaviviridae</i> family is represented by four genera comprising 89 known virus species. There are no effective therapies available against many pathogenic flaviviruses. One of the promising strategies for flavivirus infections prevention and therapy is the use of neutralizing antibodies (NAb) that can disable the virus particles from infecting the host cells. The envelope protein (E protein) of flaviviruses is a three-domain structure that mediates the fusion of viral and host membranes delivering the infectious material. We previously developed and characterized 10H10 mAb which interacts with the E protein of the tick-borne encephalitis virus (TBEV) and many other flaviviruses’ E proteins. The aim of this work was to analyze the structure of E protein binding sites recognized by the 10H10 antibody, which is reactive with different flavivirus species. Here, we present experimental data and 3D modeling indicating that the 10H10 antibody recognizes the amino acid sequence between the two cysteines C92-C116 of the fusion loop (FL) region of flaviviruses’ E proteins. Overall, our results indicate that the antibody-antigen complex can form a rigid or dynamic structure that provides antibody cross reactivity and efficient interaction with the fusion loop of E protein.https://www.mdpi.com/1422-0067/23/14/7721flavivirusTBEVWNVZIKVDENVmonoclonal antibody |
| spellingShingle | Daniil V. Shanshin Sophia S. Borisevich Alexander A. Bondar Yuri B. Porozov Elena A. Rukhlova Elena V. Protopopova Nikita D. Ushkalenko Valery B. Loktev Andrei I. Chapoval Alexander A. Ilyichev Dmitriy N. Shcherbakov Can Modern Molecular Modeling Methods Help Find the Area of Potential Vulnerability of Flaviviruses? International Journal of Molecular Sciences flavivirus TBEV WNV ZIKV DENV monoclonal antibody |
| title | Can Modern Molecular Modeling Methods Help Find the Area of Potential Vulnerability of Flaviviruses? |
| title_full | Can Modern Molecular Modeling Methods Help Find the Area of Potential Vulnerability of Flaviviruses? |
| title_fullStr | Can Modern Molecular Modeling Methods Help Find the Area of Potential Vulnerability of Flaviviruses? |
| title_full_unstemmed | Can Modern Molecular Modeling Methods Help Find the Area of Potential Vulnerability of Flaviviruses? |
| title_short | Can Modern Molecular Modeling Methods Help Find the Area of Potential Vulnerability of Flaviviruses? |
| title_sort | can modern molecular modeling methods help find the area of potential vulnerability of flaviviruses |
| topic | flavivirus TBEV WNV ZIKV DENV monoclonal antibody |
| url | https://www.mdpi.com/1422-0067/23/14/7721 |
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