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- Title
Antiviral Mechanisms of N -Phenyl Benzamides on Coxsackie Virus A9.
- Authors
Laajala, Mira; Kalander, Kerttu; Consalvi, Sara; Amamuddy, Olivier Sheik; Bishop, Özlem Tastan; Biava, Mariangela; Poce, Giovanna; Marjomäki, Varpu
- 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.
- Subjects
COXSACKIEVIRUSES; CHEMICAL libraries; DRUG efficacy; BENZAMIDE; VIRION; BINDING sites
- Publication
Pharmaceutics, 2023, Vol 15, Issue 3, p1028
- ISSN
1999-4923
- Publication type
Article
- DOI
10.3390/pharmaceutics15031028