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

Scorpions are ancient terrestrial creatures that have lived on earth for more than four hundred million years. For the sake of predation and survival, they have evolved unique venom systems containing neurotoxins, antimicrobial peptides, enzymes and other components. Natural AMPs from scorpion venoms and their derivative peptides have exhibited attractive antiviral activities, and some of these peptides have been studied in previous reports. The recombinant peptide scorpine (RScp) has been reported to inhibit Dengue-2 replication in C6/36 cells [11] . A natural amphipathic α-helical peptide Hp1090 can directly interact with the HCV viral envelope and decrease viral infectivity [12] . The scorpion venom-derived synthetic peptide mucroporin-M1 exhibited virucidal activities against measles, SARS-CoV and influenza H5N1 viruses via a direct interaction with virus envelope [13] . Mucroporin-M1 also inhibited HBV replication in vitro and in vivo by activating the mitogen-activated protein kinase (MAPK) pathway and then reducing the expression of hepatocyte nuclear factor 4α (HNF4α) [14] . Kn2-7, a scorpion venom peptide derivative, can inhibit HIV-1 by direct interactions with viral particles [15] . Histidine-rich mutants of another scorpion-derived peptide, Ctry2459, showed significantly enhanced bioavailability and anti-HCV activity [16] . Two scorpion venom peptides, Hp1036 and Hp1239, inhibited HSV-1 [17] . Recently, a scorpion defensin, BmKDfsin4, was reported to inhibit HBV replication in vitro [18] . Thus, the scorpion-derived AMP library is a rich source of new antiviral agents that are still awaiting further utilization.