Why are HIV-1 fusion inhibitors not effective against SARS-CoV? Biophysical evaluation of molecular interactions.
Why are HIV-1 fusion inhibitors not effective against SARS-CoV? Biophysical evaluation of molecular interactions.
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DOI：
10.1016/j.bbagen.2005.10.001
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发表时间：
2006-01
期刊：
影响因子：
--
通讯作者：
Castanho MA
中科院分区：
文献类型：
--
作者：
Veiga S;Yuan Y;Li X;Santos NC;Liu G;Castanho MA
严重急性呼吸综合征相关冠状病毒（SARS-CoV）的囊膜刺突（S）糖蛋白介导病毒进入靶细胞。最近的研究指出，这种病毒的细胞进入机制类似于其他包膜病毒，如HIV-1。与其他病毒肽融合抑制剂一样，SARS-CoV S蛋白HR 2衍生肽是抗病毒的潜在治疗药物。据信，HR 2肽通过与HR 1区相互作用阻断六螺旋束形成，六螺旋束是病毒融合中的关键结构。考虑到两种病毒之间的相似性，HIV-1 gp 41 HR 2衍生肽T20（恩夫韦肽）是否可能成为SARS冠状病毒抑制剂是一个讨论的问题。我们测试了T20（HIV-1 gp 41 HR 2衍生肽）和T-1249与S蛋白HR 1和HR 2衍生肽之间相互作用的可能性。我们的生物物理数据显示了SARS冠状病毒HR 1衍生肽和T20之间的显着相互作用。然而，这种相互作用只是中等程度的（KB =（1.1 ± 0.3）× 105 M−1）。这一发现表明，已经批准用于艾滋病治疗的T20可以抑制SARS-CoV与靶细胞融合的假设背后的推理是正确的，但效果可能不够强。
The envelope spike (S) glycoprotein of the severe acute respiratory syndrome associated coronavirus (SARS-CoV) mediates the entry of the virus into target cells. Recent studies point out to a cell entry mechanism of this virus similar to other enveloped viruses, such as HIV-1. As it happens with other viruses peptidic fusion inhibitors, SARS-CoV S protein HR2-derived peptides are potential therapeutic drugs against the virus. It is believed that HR2 peptides block the six-helix bundle formation, a key structure in the viral fusion, by interacting with the HR1 region. It is a matter of discussion if the HIV-1 gp41 HR2-derived peptide T20 (enfuvirtide) could be a possible SARS-CoV inhibitor given the similarities between the two viruses. We tested the possibility of interaction between both T20 (HIV-1 gp41 HR2-derived peptide) and T-1249 with S protein HR1- and HR2-derived peptides. Our biophysical data show a significant interaction between a SARS-CoV HR1-derived peptide and T20. However, the interaction is only moderate (KB = (1.1 ± 0.3) × 105 M−1). This finding shows that the reasoning behind the hypothesis that T20, already approved for clinical application in AIDS treatment, could inhibit the fusion of SARS-CoV with target cells is correct but the effect may not be strong enough for application.
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影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
11.4
作者：
Cladera, J;Martin, I;O'Shea, P
通讯作者：
O'Shea, P
DOI：
10.1016/s0140-6736(03)13077-2
发表时间：
2003-04-19
期刊：
Lancet (London, England)
影响因子：
--
作者：
Peiris JS;Lai ST;Poon LL;Guan Y;Yam LY;Lim W;Nicholls J;Yee WK;Yan WW;Cheung MT;Cheng VC;Chan KH;Tsang DN;Yung RW;Ng TK;Yuen KY;SARS study group
通讯作者：
SARS study group
DOI：
10.1034/j.1399-3011.2003.00039.x
发表时间：
2003-03-01
期刊：
JOURNAL OF PEPTIDE RESEARCH
影响因子：
--
作者：
Ganesh, S;Jayakumar, R
通讯作者：
Jayakumar, R
DOI：
10.1073/pnas.0400576101
发表时间：
2004-06-01
影响因子：
11.1
作者：
Bosch, BJ;Martina, BEE;Rottier, PJM
通讯作者：
Rottier, PJM