Novel amodiaquine derivatives potently inhibit Ebola virus infection.
Novel amodiaquine derivatives potently inhibit Ebola virus infection.
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新型阿莫地喹衍生物可有效抑制埃博拉病毒感染。
DOI：
10.1016/j.antiviral.2018.10.025
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发表时间：
2018
影响因子：
7.6
通讯作者：
Davey,RobertA
中科院分区：
文献类型：
--
作者：
Sakurai,Yasuteru;Sakakibara,Norikazu;Toyama,Masaaki;Baba,Masanori;Davey,RobertA
Ebola virus disease is a severe disease caused by highly pathogenicEbolaviruses. Although it shows a high mortality rate in humans, currently there is no licensed therapeutic. During the recent epidemic in West Africa, it was demonstrated that administration of antimalarial medication containing amodiaquine significantly lowered mortality rate of patients infected with the virus. Here, in order to improve its antiviral activity, a series of amodiaquine derivatives were synthesized and tested for Ebola virus infection. We found that multiple compounds were more potent than amodiaquine. The structure-activity relationship analysis revealed that the two independent parts, which are the alkyl chains extending from the aminomethyl group and a halogen bonded to the quinoline ring, were keys for enhancing antiviral potency without increasing toxicity. When these modifications were combined, the antiviral efficacy could be further improved with the selectivity indexes being over 10-times higher than amodiaquine. Mechanistic evaluation demonstrated that the potent derivatives blocked host cell entry of Ebola virus, like the parental amodiaquine. Taken together, our work identified novel potent amodiaquine derivatives, which will aid in further development of effective antiviral therapeutics.
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