A1 Journal article (refereed)
Antiviral Mechanisms of N-Phenyl Benzamides on Coxsackie Virus A9 (2023)
Laajala, M., Kalander, K., Consalvi, S., Amamuddy, O. S., Bishop, Ö. T., Biava, M., Poce, G., & Marjomäki, V. (2023). Antiviral Mechanisms of N-Phenyl Benzamides on Coxsackie Virus A9. Pharmaceutics, 15(3), Article 1028. https://doi.org/10.3390/pharmaceutics15031028
JYU authors or editors
Publication details
All authors or editors: Laajala, Mira; Kalander, Kerttu; Consalvi, Sara; Amamuddy, Olivier Sheik; Bishop, Özlem Tastan; Biava, Mariangela; Poce, Giovanna; Marjomäki, Varpu
Journal or series: Pharmaceutics
eISSN: 1999-4923
Publication year: 2023
Publication date: 22/03/2023
Volume: 15
Issue number: 3
Article number: 1028
Publisher: MDPI AG
Publication country: Switzerland
Publication language: English
DOI: https://doi.org/10.3390/pharmaceutics15031028
Publication open access: Openly available
Publication channel open access: Open Access channel
Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/86147
Abstract
Enteroviruses are one of the most abundant groups of viruses infecting humans, and yet there are no approved antivirals against them. To find effective antiviral compounds against enterovirus B group viruses, an in-house chemical library was screened. The most effective compounds against Coxsackieviruses B3 (CVB3) and A9 (CVA9) were CL212 and CL213, two N-phenyl benzamides. Both compounds were more effective against CVA9 and CL213 gave a better EC50 value of 1 µM with high a specificity index of 140. Both drugs were most effective when incubated directly with viruses suggesting that they mainly bound to the virions. A real-time uncoating assay showed that the compounds stabilized the virions and radioactive sucrose gradient as well as TEM confirmed that the viruses stayed intact. A docking assay, taking into account larger areas around the 2-and 3-fold axes of CVA9 and CVB3, suggested that the hydrophobic pocket gives the strongest binding to CVA9 but revealed another binding site around the 3-fold axis which could contribute to the binding of the compounds. Together, our data support a direct antiviral mechanism against the virus capsid and suggest that the compounds bind to the hydrophobic pocket and 3-fold axis area resulting in the stabilization of the virion.
Keywords: viruses; enteroviruses; capsid; communicable diseases
Free keywords: enterovirus; antiviral; capsid binder; N-phenyl benzamide
Contributing organizations
Related projects
- Fighting COVID19 with calpain inhibitors
- Marjomäki, Varpu
- Research Council of Finland
Ministry reporting: Yes
Reporting Year: 2023
Preliminary JUFO rating: 1