Anti-HIV-1 Activity of a New Scorpion Venom Peptide Derivative Kn2-7

Yaoqing Chen,Benxia He,Fang Liu,Wei Shi,Yan Zhang,Zhijian Cao,Jie Yu,Yaoming Li,Luyang Cao,Wenxin Li,Jingyi Yang,Maohua Zhong,Huimin Yan,Yuan Cao,Chen Han,Deying Guo,Dihan Zhou,Qiaoli Li,Ying Sun

doi:10.1371/journal.pone.0034947

Yaoqing Chen, Benxia He + Show 17 more

Open Access

https://doi.org/10.1371/journal.pone.0034947

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Abstract

For over 30 years, HIV/AIDS has wreaked havoc in the world. In the absence of an effective vaccine for HIV, development of new anti-HIV agents is urgently needed. We previously identified the antiviral activities of the scorpion-venom-peptide-derived mucroporin-M1 for three RNA viruses (measles viruses, SARS-CoV, and H5N1). In this investigation, a panel of scorpion venom peptides and their derivatives were designed and chosen for assessment of their anti-HIV activities. A new scorpion venom peptide derivative Kn2-7 was identified as the most potent anti-HIV-1 peptide by screening assays with an EC50 value of 2.76 µg/ml (1.65 µM) and showed low cytotoxicity to host cells with a selective index (SI) of 13.93. Kn2-7 could inhibit all members of a standard reference panel of HIV-1 subtype B pseudotyped virus (PV) with CCR5-tropic and CXCR4-tropic NL4-3 PV strain. Furthermore, it also inhibited a CXCR4-tropic replication-competent strain of HIV-1 subtype B virus. Binding assay of Kn2-7 to HIV-1 PV by Octet Red system suggested the anti-HIV-1 activity was correlated with a direct interaction between Kn2-7 and HIV-1 envelope. These results demonstrated that peptide Kn2-7 could inhibit HIV-1 by direct interaction with viral particle and may become a promising candidate compound for further development of microbicide against HIV-1.

Highlights

34 million people were living with human immunodeficiency virus (HIV) at the end of 2010 in the globe [1] and half of them were women
Five scorpion venom peptides and their derivatives were screened for their anti-HIV-1 activities, and the results showed that three of them exhibited potent anti-HIV-1 activity, in which Kn2-7 showed the highest level of anti-HIV-1 activity
The results showed that mucroporin-M1, BmKn2 and Kn2-7 could significantly decrease infectivity of an HIV-1 clade B b12-resistant pseudotyped virus CAAN5342 compare to the mucroporin, mucroporin-S1, BSA and no-peptide virus mock control, in which peptide Kn2-7 showed the highest level of anti-HIV-1 activity and almost completely inhibited viral infection (Fig. 1)

Summary

Introduction

34 million people were living with human immunodeficiency virus (HIV) at the end of 2010 in the globe [1] and half of them were women. There are still no effective vaccine or other countermeasure to eliminate HIV transmission [2]. HIV virus spreads fast and the HIV/AIDS pandemic still stands as a serious public health problem worldwide [1]. Current situation clearly indicates the necessity of developing new anti-HIV agents which can be used for prevention of HIV/AIDS dissemination. HIV-1 initially infects T cells through CD4 receptor [5] and either of the two chemokine co-receptors CXCR4 (X4) or CCR5 (R5) (or both) [6,7,8]. Some microbicides tested can inhibit infection by X4-tropic HIV1 but insufficiently inhibit R5-tropic HIV-1 to the same extent [9,10]. Effectiveness, safety and broad spectrum are very important to an anti-HIV microbicide.

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