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Design and evaluation of antiretroviral peptides corresponding to the C-terminal heptad repeat region (C-HR) of human immunodeficiency virus type 1 envelope glycoprotein gp41 |
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| Authors: | Bongkot Soonthornsata Yu-Shi Tian Piraporn Utachee Panasda Isarangkura-na-ayuthaya Tatsuya Takagi Kazuyoshi Ikuta Pathom Sawanpanyalert Masanori Kameoka |
| Affiliation: | a Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections (RCC-ERI)2, Nonthaburi, Thailand b Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan c National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand d Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan |
| Abstract: | Two α-helical heptad repeats, N-HR and C-HR, located in the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41, play an important role in membrane fusion by forming a 6-helix bundle. C34, a peptide mimicking C-HR, inhibits the formation of the 6-helix bundle; thus, it has potential as a novel antiretroviral compound. In order to improve the inhibitory effect of C34 on HIV-1 replication, we designed new C34-derived peptides based on computational analysis of the stable conformation of the 6-helix bundle. Newly designed peptides showed a stronger inhibitory effect on the replication of recombinant viruses containing CRF01_AE, subtype B or subtype C Env than C34 or a fusion inhibitor, T-20. In addition, these peptides inhibited the replication of a T-20-resistant virus. We propose that these peptides could be applied to develop novel antiretroviral compounds to inhibit the replication of various subtypes of HIV-1 as well as of T-20-resistant variants. |
| Keywords: | HIV-1 Envelope glycoprotein gp41 α-helical heptad repeat C34 fusion inhibitor CRF01_AE Subtypes |
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