Inhibition of Chikungunya Virus Infection by 4-Hydroxy-1-Methyl-3-(3-morpholinopropanoyl)quinoline-2(1H)-one (QVIR) Targeting nsP2 and E2 Proteins.

作者: Mohammad Islamuddin , Mohammad Islamuddin , Obaid Afzal , Wajihul Hasan Khan , Kentaro Kato

DOI: 10.1021/ACSOMEGA.1C00447

关键词:

摘要: The re-emergence of Chikungunya virus (CHIKV) infection in humans with no approved antiviral therapies or vaccines is one the major problems global significance. In present investigation, we screened 80 in-house quinoline derivatives for their anti-CHIKV activity by computational techniques and found 4-hydroxy-1-methyl-3-(3-morpholinopropanoyl)quinoline-2(1H)-one (QVIR) to have potential binding affinities CHIKV nsP2 E2 glycoproteins. QVIR was evaluated vitro its potential. showed strong inhibition an EC50 (50% effective concentration) value 2.2 ± 0.49 μM without significant cytotoxicity (CC50 > 200 μM) chosen further elucidation mechanism. infectious viral particle formation abolished approximately 72% at a concentration 20 during BHK-21 cell line, RNA synthesis diminished 84% as well 74% E2, whereas levels proteins were decreased 69.9% 53.9% E2. Flow cytometry analysis confirmed huge decline expression 71.84 67.7%, respectively. Time addition experiments indicated that inhibited early late stages replication cycle, optimal observed 16 h post infection. study advocates first time acts substantial potent inhibitor against might be auspicious novel drug candidate development therapeutic agents infections.

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