2. Academic Validation
  3. (+)-fenchol and (-)-isopinocampheol derivatives targeting the entry process of filoviruses

(+)-fenchol and (-)-isopinocampheol derivatives targeting the entry process of filoviruses

  • Eur J Med Chem. 2024 Sep 5:275:116596. doi: 10.1016/j.ejmech.2024.116596.
Anastasiya S Sokolova 1,  Dmitriy S Baev 2,  Ekaterina D Mordvinova 3,  Olga I Yarovaya 4,  Natalia V Volkova 3,  Dmitriy N Shcherbakov 3,  Alina A Okhina 4,  Artem D Rogachev 4,  Tatiana A Shnaider 5,  Anastasiya S Chvileva 6,  Tatiana V Nikitina 7,  Tatyana G Tolstikova 4,  Nariman F Salakhutdinov 4
Affiliations

Affiliations

  • 1 N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, 630090, Russian Federation. Electronic address: asokolova@nioch.nsc.ru.
  • 2 N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, 630090, Russian Federation; SRF SKIF, Koltsovo, Novosibirsk Oblast, 630559, Russian Federation.
  • 3 State Research Center of Virology and Biotechnology VECTOR (Rospotrebnadzor), Koltsovo, Novosibirsk Oblast, 630559, Russian Federation.
  • 4 N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, 630090, Russian Federation.
  • 5 Institute of Cytology and Genetics (ICG), SB RAS, Novosibirsk, 630090, Russian Federation.
  • 6 Novosibirsk State University, Novosibirsk, 630090, Russian Federation.
  • 7 Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 634050, Russian Federation.
PMID: 38889610 DOI: 10.1016/j.ejmech.2024.116596
Abstract

The increasing frequency of Filovirus outbreaks in African countries has led to a pressing need for the development of effective antifilovirus agents. In continuation of our previous research on the antifilovirus activity of monoterpenoid derivatives, we synthesized a series of (+)-fenchol and (-)-isopinocampheol derivatives by varying the type of heterocycle and linker length. Derivatives with an N-alkylpiperazine cycle proved to be the most potent Antiviral compounds, with half-maximal inhibitory concentration (IC50) 1.4-20 μМ against Lenti-EboV-GP Infection and 11.3-47 μМ against Lenti-MarV-GP Infection. Mechanism-of-action experiments revealed that the compounds may exert their action by binding to surface glycoproteins (GPs). It was demonstrated that the binding of the synthesized compounds to the Marburg virus GP is less efficient as compared to the Ebola virus GP. Furthermore, it was shown that the compounds possess lysosomotropic properties. Thus, the Antiviral activity may be due to dual effects. This study offers new Antiviral agents that are worthy of further exploration.

Keywords

Ebola virus; Fenchol; Glycoprotein; Isopinocampheol; Lysosomotropic compounds; Marburg virus.

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