Key result
Quinoline analogues demonstrate improved in vitro potency and high selectivity against EV-D68 vs dibucaine.
Why the study?
No approved vaccine or antiviral exists for EV-D68, prompting efforts to improve the antiviral potency and selectivity of the inhibitor dibucaine.
Newly synthesized quinoline analogues (10a, 12a, and 12c) show potent and selective in vitro antiviral activity against EV-D68, suggesting potential for developing treatments for respiratory and neuronal infections.
Answers are grounded in this paper and cite their sources.
Improved EV-D68 leads show submicromolar potency in vitro; leaves open advancement to in vivo and clinical testing.
Enterovirus D68 (EV-D68) is an atypical nonpolio enterovirus that mainly infects the respiratory system of humans, leading to moderate-to-severe respiratory diseases. In rare cases, EV-D68 can spread to the central nervous system and cause paralysis in infected patients, especially young children and immunocompromised individuals. There is currently no approved vaccine or antiviral available for the prevention and treatment of EV-D68. In this study, we aimed to improve the antiviral potency and selectivity of a previously reported EV-D68 inhibitor, dibucaine, through structure–activity relationship studies. In total, 60 compounds were synthesized and tested against EV-D68 using the viral cytopathic effect assay. Three compounds 10a, 12a, and 12c were identified to have significantly improved potency (EC 50 < 1 μM) and a high selectivity index (>180) compared with dibucaine against five different strains of EV-D68 viruses. These compounds also showed potent antiviral activity in neuronal cells, such as A172 and SH-SY5Y cells, suggesting they might be further developed for the treatment of both respiratory infection as well as neuronal infection.
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Musharrafieh et al. (2019) studied Enterovirus D68 (EV-D68) infection. Quinoline analogues (compounds 10a, 12a, and 12c) vs. dibucaine was evaluated on Antiviral potency (EC50) and selectivity index against EV-D68. Quinoline analogues 10a, 12a, and 12c demonstrated significantly improved antiviral potency (EC50 < 1 μM) and high selectivity (>180) against EV-D68 compared with dibucaine in vitro.
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