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Expanding the antiviral arsenal: N-arylated 1,2,4-oxadiazol-5(4H)-ones show high activity against orthopoxviruses. / Semenov, Artem V.; Baykov, Sergey V.; Soldatova, Natalia S. и др.

в: European Journal of Medicinal Chemistry, Том 300, 118124, 15.12.2025, стр. 118124.

Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование

Harvard

Semenov, AV, Baykov, SV, Soldatova, NS, Geyl, KK, Shetnev, AA, Boyarskiy, VP, Yusubov, MS, Bormotov, NI, Serova, OA, Shishkina, LN, Ovchinnikova, AS, Odnoshevsky, DA, Pyankov, OV, Borisevich, SS, Gorohov, YV, Nikitin, VN, Shcherbakov, DN, Yarovaya, OI, Salakhutdinov, NF & Postnikov, PS 2025, 'Expanding the antiviral arsenal: N-arylated 1,2,4-oxadiazol-5(4H)-ones show high activity against orthopoxviruses', European Journal of Medicinal Chemistry, Том. 300, 118124, стр. 118124. https://doi.org/10.1016/j.ejmech.2025.118124

APA

Semenov, A. V., Baykov, S. V., Soldatova, N. S., Geyl, K. K., Shetnev, A. A., Boyarskiy, V. P., Yusubov, M. S., Bormotov, N. I., Serova, O. A., Shishkina, L. N., Ovchinnikova, A. S., Odnoshevsky, D. A., Pyankov, O. V., Borisevich, S. S., Gorohov, Y. V., Nikitin, V. N., Shcherbakov, D. N., Yarovaya, O. I., Salakhutdinov, N. F., & Postnikov, P. S. (2025). Expanding the antiviral arsenal: N-arylated 1,2,4-oxadiazol-5(4H)-ones show high activity against orthopoxviruses. European Journal of Medicinal Chemistry, 300, 118124. [118124]. https://doi.org/10.1016/j.ejmech.2025.118124

Vancouver

Semenov AV, Baykov SV, Soldatova NS, Geyl KK, Shetnev AA, Boyarskiy VP и др. Expanding the antiviral arsenal: N-arylated 1,2,4-oxadiazol-5(4H)-ones show high activity against orthopoxviruses. European Journal of Medicinal Chemistry. 2025 дек. 15;300:118124. 118124. Epub 2025 сент. 8. doi: 10.1016/j.ejmech.2025.118124

Author

Semenov, Artem V. ; Baykov, Sergey V. ; Soldatova, Natalia S. и др. / Expanding the antiviral arsenal: N-arylated 1,2,4-oxadiazol-5(4H)-ones show high activity against orthopoxviruses. в: European Journal of Medicinal Chemistry. 2025 ; Том 300. стр. 118124.

BibTeX

@article{c4a217224efa42319439f65a1980d046,
title = "Expanding the antiviral arsenal: N-arylated 1,2,4-oxadiazol-5(4H)-ones show high activity against orthopoxviruses",
abstract = "The study presents the discovery of a novel class of N-arylated 1,2,4-oxadiazol-5(4H)-ones as potent inhibitors of orthopoxviruses, including the variola virus (VARV). Through systematic structural modifications, two lead compounds, 4 (4-CF3/4-NO2) and 10 (4-I/4-NO2), demonstrated in submicromolar concentration antiviral activity against Vaccinia virus (VACV), cowpox virus (CPXV), ectromelia virus (ECTV), and VARV, with selectivity indices (SI) up to 13738. Studies of mechanisms of action, including time-of-addition experiments and molecular modeling, have shown that these compounds can target the conserved protein p37, which plays a key role in the envelope of the virus. Furthermore, bioinformatic analysis revealed potential interactions with late-stage replication proteins encoded by the A39R and C8L genes. The synthesized derivatives showed activity higher than that of Cidofovir, although they were less effective than that of Tecovirimate. This work highlights the potential of oxadiazolone-based scaffolds as broad-spectrum antipoxviral agents that meet the unmet need for therapy against emerging and re-emerging orthopoxviral threats.",
keywords = "Antiviral activity, Bioinformatics, Cowpox virus, Molecular modeling, Mousepox virus, N-Aryl-oxadiazol-5(4H)-Ones, Orthopoxviruses, Vaccinia virus, Variola virus, p37",
author = "Semenov, {Artem V.} and Baykov, {Sergey V.} and Soldatova, {Natalia S.} and Geyl, {Kirill K.} and Shetnev, {Anton A.} and Boyarskiy, {Vadim P.} and Yusubov, {Mekhman S.} and Bormotov, {Nikolai I.} and Serova, {Olga A.} and Shishkina, {Larisa N.} and Ovchinnikova, {Alena S.} and Odnoshevsky, {Dmitrii A.} and Pyankov, {Oleg V.} and Borisevich, {Sophia S.} and Gorohov, {Yakov V.} and Nikitin, {Vladimir N.} and Shcherbakov, {Dmitry N.} and Yarovaya, {Olga I.} and Salakhutdinov, {Nariman F.} and Postnikov, {Pavel S.}",
note = "Virological studies were carried out with financial support from the State assignment of the State Research Centre of Virology and Biotechnology VECTOR. Synthetic study was supported by the Russian Science Foundation, project 21-73-20031-P. This work was partially supported by the Ministry of Science and Higher Education of the Russian Federation within the governmental order for N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS (project FWUE-2025-0006). The bioinformatic analysis was performed within the framework of the state assignment of the Ufa Institute of Chemistry UFRC RAS Kinetic, Spectral-Luminescent, and Theoretical Investigation of Key Intermediates in Chemical and Biochemical Oxidation Processes 125020601626–9. The authors are grateful to the theoretical group “Quanta and Dynamics” for theoretical study https://monrel.ru/about_en/",
year = "2025",
month = sep,
day = "8",
doi = "10.1016/j.ejmech.2025.118124",
language = "English",
volume = "300",
pages = "118124",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Science Publishing Company, Inc.",

}

RIS

TY - JOUR

T1 - Expanding the antiviral arsenal: N-arylated 1,2,4-oxadiazol-5(4H)-ones show high activity against orthopoxviruses

AU - Semenov, Artem V.

AU - Baykov, Sergey V.

AU - Soldatova, Natalia S.

AU - Geyl, Kirill K.

AU - Shetnev, Anton A.

AU - Boyarskiy, Vadim P.

AU - Yusubov, Mekhman S.

AU - Bormotov, Nikolai I.

AU - Serova, Olga A.

AU - Shishkina, Larisa N.

AU - Ovchinnikova, Alena S.

AU - Odnoshevsky, Dmitrii A.

AU - Pyankov, Oleg V.

AU - Borisevich, Sophia S.

AU - Gorohov, Yakov V.

AU - Nikitin, Vladimir N.

AU - Shcherbakov, Dmitry N.

AU - Yarovaya, Olga I.

AU - Salakhutdinov, Nariman F.

AU - Postnikov, Pavel S.

N1 - Virological studies were carried out with financial support from the State assignment of the State Research Centre of Virology and Biotechnology VECTOR. Synthetic study was supported by the Russian Science Foundation, project 21-73-20031-P. This work was partially supported by the Ministry of Science and Higher Education of the Russian Federation within the governmental order for N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS (project FWUE-2025-0006). The bioinformatic analysis was performed within the framework of the state assignment of the Ufa Institute of Chemistry UFRC RAS Kinetic, Spectral-Luminescent, and Theoretical Investigation of Key Intermediates in Chemical and Biochemical Oxidation Processes 125020601626–9. The authors are grateful to the theoretical group “Quanta and Dynamics” for theoretical study https://monrel.ru/about_en/

PY - 2025/9/8

Y1 - 2025/9/8

N2 - The study presents the discovery of a novel class of N-arylated 1,2,4-oxadiazol-5(4H)-ones as potent inhibitors of orthopoxviruses, including the variola virus (VARV). Through systematic structural modifications, two lead compounds, 4 (4-CF3/4-NO2) and 10 (4-I/4-NO2), demonstrated in submicromolar concentration antiviral activity against Vaccinia virus (VACV), cowpox virus (CPXV), ectromelia virus (ECTV), and VARV, with selectivity indices (SI) up to 13738. Studies of mechanisms of action, including time-of-addition experiments and molecular modeling, have shown that these compounds can target the conserved protein p37, which plays a key role in the envelope of the virus. Furthermore, bioinformatic analysis revealed potential interactions with late-stage replication proteins encoded by the A39R and C8L genes. The synthesized derivatives showed activity higher than that of Cidofovir, although they were less effective than that of Tecovirimate. This work highlights the potential of oxadiazolone-based scaffolds as broad-spectrum antipoxviral agents that meet the unmet need for therapy against emerging and re-emerging orthopoxviral threats.

AB - The study presents the discovery of a novel class of N-arylated 1,2,4-oxadiazol-5(4H)-ones as potent inhibitors of orthopoxviruses, including the variola virus (VARV). Through systematic structural modifications, two lead compounds, 4 (4-CF3/4-NO2) and 10 (4-I/4-NO2), demonstrated in submicromolar concentration antiviral activity against Vaccinia virus (VACV), cowpox virus (CPXV), ectromelia virus (ECTV), and VARV, with selectivity indices (SI) up to 13738. Studies of mechanisms of action, including time-of-addition experiments and molecular modeling, have shown that these compounds can target the conserved protein p37, which plays a key role in the envelope of the virus. Furthermore, bioinformatic analysis revealed potential interactions with late-stage replication proteins encoded by the A39R and C8L genes. The synthesized derivatives showed activity higher than that of Cidofovir, although they were less effective than that of Tecovirimate. This work highlights the potential of oxadiazolone-based scaffolds as broad-spectrum antipoxviral agents that meet the unmet need for therapy against emerging and re-emerging orthopoxviral threats.

KW - Antiviral activity

KW - Bioinformatics

KW - Cowpox virus

KW - Molecular modeling

KW - Mousepox virus

KW - N-Aryl-oxadiazol-5(4H)-Ones

KW - Orthopoxviruses

KW - Vaccinia virus

KW - Variola virus

KW - p37

UR - https://www.scopus.com/pages/publications/105015653493

UR - https://www.mendeley.com/catalogue/d6bed69a-74b4-3dd3-a68a-39c4af137c95/

U2 - 10.1016/j.ejmech.2025.118124

DO - 10.1016/j.ejmech.2025.118124

M3 - Article

C2 - 40946533

VL - 300

SP - 118124

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

M1 - 118124

ER -

ID: 69742841