Anti-Orthopoxvirus Activity of Amantadine and Rimantadine Derivatives—In Vitro Testing and Molecular Modeling
In 2022, the number of mpox cases spiked worldwide, leading to a surge in scientific research on members of the Orthopoxvirus genus and the discovery of new compounds exhibiting anti-orthopoxvirus activity. This work is devoted to the synthesis of compounds containing an adamantane fragment and the evaluation of their activity against the vaccinia virus, offering a possible mechanism of the antiviral action of the synthesized agents. Among all the studied adamantane derivatives, three compounds (2, 4, and 12) were found to demonstrate the highest antiviral activity, with the most promising compound 2 (N-(adamantan-1-yl)isonicotinamide) having the lowest toxicity level with a selectivity index (SI) of 115. The pharmacophoric profiles of these compounds are similar to the pharmacophoric profile of tecovirimat, an inhibitor of the membrane viral protein p37. Analysis of the results of molecular modeling suggests that the investigated compounds can inhibit the vaccinia virus by suppressing the phospholipase activity of membrane viral protein p37.
Authors
- Olga А. Serova
- Е. А. Дикусар (ORCID: https://orcid.org/0000-0002-3868-1871)
- Alexey Yu. Fedorov (ORCID: https://orcid.org/0000-0002-1933-5770)
- В. И. Поткин (ORCID: https://orcid.org/0000-0003-0250-837X)
- Оlga I. Yarovaya (ORCID: https://orcid.org/0000-0002-2333-4893)
- Shishkina Ln (ORCID: https://orcid.org/0000-0002-8264-0217)
- Sophia S. Borisevich (ORCID: https://orcid.org/0000-0001-8481-0470)
- Sergey G. Arkhipov (ORCID: https://orcid.org/0000-0003-4812-3037)
- Е. А. Akishina (ORCID: https://orcid.org/0000-0002-0803-8623)
- Нариман Ф. Салахутдинов (ORCID: https://orcid.org/0000-0001-8512-4309)
- Э. М. Хамитов (ORCID: https://orcid.org/0000-0001-8987-4254)
- Ivan A. Moskalev (ORCID: https://orcid.org/0009-0000-4050-5781)
- Nikolay I. Bormotov
Institutions
- National Academy of Sciences of Belarus (BY)
- State Research Center of Virology and Biotechnology VECTOR (RU)
- Novosibirsk Institute of Organic Chemistry (RU)
- Ufa Institute of Chemistry (RU)
- Siberian Branch of the Russian Academy of Sciences (RU)
Publication Details
- Journal
- Chemistry
- Published
- 2025-03-01
- DOI
- https://doi.org/10.3390/chemistry7020034
- Citations
- 3
- Primary Topic
- Herpesvirus Infections and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 4.06
Funders
- Ministry of Science and Higher Education of the Russian Federation