Studies on Inhibition of Proliferation of Enterovirus-71 by Compound YZ-LY-0

分类： 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间： 2016-05-11

Yang, Qingzhan Shaw, Neil Rao, Zihe Lou, Zhiyong Jie, Qing Shaw, Neil Rao, Zihe Yin, Zheng Yin, Zheng Yin, Zheng Li, Lei Rao, Zihe Lou, Zhiyong Li, Lei Rao, Zihe Lou, Zhiyong Li, Lei Rao, Zihe Lou, Zhiyong

摘要： In recent years, hand-foot-and-mouth disease (HFMD), which is caused by Enteroviruses, has emerged as a serious illness. It affects mainly children under the age of five and results in high fatality rates. Enterovirus 71 (EV71) is the main causative agent of HFMD in China and currently there are no effective anti-viral drugs available to treat HFMD. In the present study, we screened compounds for inhibition of proliferation of EV71. Compound YZ-LY-0 stalled the life cycle of EV71. The inhibitor exhibited EC50 value of 0.29 mu m against SK-EV006 strain of EV71. Notably, YZ-LY-0 had low cytotoxicity (CC50 > 100 mu M) and a high selectivity index (over 300) in Vero and RD cells. YZ-LY-0 in combination with an EV71 RdRp inhibitor or an entry inhibitor showed an antagonistic effect at very low concentrations. However, at higher concentrations the inhibitors exhibited a synergistic effect in inhibiting viral replication. Preliminary results on investigation of the mechanism of inhibition indicate that YZ-LY-0 does not block the entry of the virus in the host cell, but instead inhibits an early stage of EV71 replication. Our studies provide a potential clinical therapeutic option against EV71 infections and suggest that a combined application of YZ-LY-0 with other inhibitors could be more effective in the treatment of HFMD.

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