Histidine-rich Modification of a Scorpion-derived Peptide Improves Bioavailability and Inhibitory Activity against HSV-1

Zeng, Zhengyang; Zhang, Runhong; Hong, Wei; Cheng, Yuting; Wang, Huijuan; Lang, Yange; Ji, Zhenglin; Wu, Yingliang; Li, Wenxin; Xie, Youli; Cao, Zhijian

The cytotoxicities of the Eval418 derivative peptides to Vero cells were evaluated by MTT assay (Figure 6a ). The CC 50 values for Eval418-FH2, Eval418-FH3, Eval418-FH4 and Eval418-FH5 were 27.60, 26.83, 27.58 and 106.68 μg/mL, respectively, indicating that Eval418-FH5 had a lower cytotoxicity than the wild type peptide and other derivatives. The modes of action for these derivative peptides were identified by time of addition experiments as described previously (Figure 6b ). All four derivative peptides maintained inhibitory activities against HSV-1 proliferation when pre-incubated with HSV-1 and added to cells at the viral attachment step. In addition, these derivative peptides showed greater inhibition of viral entry than did the wild type peptide Eval418. Interestingly, the derivative peptides also reduced plaque formation in PRA experiments when added to the cells at 5 μg/mL after HSV-1 infection. The inhibitory rates were 21.34%, 24.07%, 21.83% and 29.72%, respectively, whereas the wild type peptide Eval418 hardly exerted such an effect.