Anti-HIV-1 activity of a new scorpion venom peptide derivative Kn2-7.
Anti-HIV-1 activity of a new scorpion venom peptide derivative Kn2-7.
复制标题
DOI：
10.1371/journal.pone.0034947
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yan H
中科院分区：
文献类型：
--
作者：
Chen Y;Cao L;Zhong M;Zhang Y;Han C;Li Q;Yang J;Zhou D;Shi W;He B;Liu F;Yu J;Sun Y;Cao Y;Li Y;Li W;Guo D;Cao Z;Yan H
30多年来，艾滋病在全球肆虐。在缺乏有效的艾滋病毒疫苗的情况下，迫切需要开发新的抗艾滋病毒药物。我们先前确定了蝎毒肽衍生的微孔蛋白m1对三种RNA病毒（麻疹病毒、SARS-CoV和H5N1）的抗病毒活性。在这项研究中，设计和选择了一组蝎子毒液肽及其衍生物，以评估其抗hiv活性。经筛选鉴定，蝎毒肽衍生物Kn2-7为最有效的抗hiv -1肽，EC50值为2.76µg/ml(1.65µM)，对宿主细胞具有较低的细胞毒性，选择性指数（SI）为13.93。Kn2-7能抑制嗜ccr5和嗜cxcr4的NL4-3型HIV-1亚型B伪病毒（PV）的所有标准参比组成员。此外，它还抑制了HIV-1亚型B病毒嗜cxcr4复制能力强的毒株。用Octet Red系统对Kn2-7与HIV-1蛋白的结合试验表明，其抗HIV-1活性与Kn2-7与HIV-1包膜的直接相互作用有关。这些结果表明，肽Kn2-7可以通过与病毒颗粒的直接相互作用来抑制HIV-1，可能成为进一步开发抗HIV-1杀菌剂的候选化合物。
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.
登录
查看更多内容
影响因子：
56.9
作者：
Feng, Y;Broder, CC;Berger, EA
通讯作者：
Berger, EA
影响因子：
16.2
作者：
CORY, AH;OWEN, TC;CORY, JG
通讯作者：
CORY, JG
影响因子：
2.9
作者：
Abdiche, Yasmina;Malashock, Dan;Pons, Jaurne
通讯作者：
Pons, Jaurne
影响因子：
64.8
作者：
Deng, HK;Liu, R;Landau, NR
通讯作者：
Landau, NR
影响因子：
168.9
作者：
Buchbinder, Susan P.;Mehrotra, Devon V.;Duerr, Ann;Fitzgerald, Daniel W.;Mogg, Robin;Li, David;Gilbert, Peter B.;Lama, Javier R.;Marmor, Michael;del Rio, Carlos;McElrath, M. Juliana;Casimiro, Danilo R.;Gottesdiener, Keith M.;Chodakewitz, Jeffrey A.;Corey, Lawrence;Robertson, Michael N.
通讯作者：
Robertson, Michael N.