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

In the past decades, many antiviral peptides have been discovered or designed, and most have exerted potential virucidal activities. However, the greatest difficulty in treating viral diseases is the clearance of established infection in most natural and clinical conditions. However, the lipophilic muramyl peptide MTP-PE has been reported as a potent inhibitor of HIV replication in macrophages [23] . NP-1, a rabbit α-defensin, can simultaneously prevent the entry and intercellular spread of HSV-2 [24] . The derivative virucidal peptide, C5A, exhibits antiviral activities against HCV, HIV-1 and HSV-1 by disturbing viral membranes. In addition, C5A can block viral entry and suppress established infection [25] [26] [27] . Our group also has completed several studies of antiviral peptides that can inhibit established viral infection. Anti-HBV experiments demonstrated that a scorpion-derived short linear peptide, mucroporin-M1, can inhibit HBV replication in vitro and in vivo by activating the MAPK pathway and down-regulating HNF4α expression [14] . Designed histidine-rich peptides from the template of the scorpion venom peptide Ctry2459 showed considerable inhibition against HCV RNA when added at 4 h, 24 h and 48 h after infection [16] . The scorpion defensin BmKDfsin4 can inhibit HBV replication in vitro [18] and also showed ion-channel blocking activity and antibacterial activity in another study by us [28] .