Discovery of Quinoline Analogues as Potent Antivirals against Enterovirus D68 (EV-D68)

Rami Musharrafieh, Jiantao Zhang, Peter Tuohy, Naoya Kitamura, Shreya Sai Bellampalli, Yanmei Hu, Rajesh Khanna, Jun Wang

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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 (EC50 < 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.

Original languageEnglish (US)
Pages (from-to)4074-4090
Number of pages17
JournalJournal of Medicinal Chemistry
Volume62
Issue number8
DOIs
StatePublished - Apr 25 2019

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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