Cloaked similarity between HIV-1 and SARS-CoV suggests an anti-SARS strategy.

Cloaked similarity between HIV-1 and SARS-CoV suggests an anti-SARS strategy.
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DOI:
10.1186/1471-2180-3-20
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发表时间:
2003-09-21
期刊:
影响因子:
4.2
通讯作者:
Levanon EY
Levanon EY
中科院分区:
生物学3区
文献类型:
--
作者:
Kliger Y;Levanon EY

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严重急性呼吸道综合征(SARS)是一种发热性呼吸道疾病。这种疾病在病原学上与一种新的冠状病毒有关,这种冠状病毒被命名为SARS相关冠状病毒(SARS-CoV),其基因组最近被测序。由于它是冠状病毒科的成员,其刺突蛋白(S2)被认为通过促进病毒和宿主细胞膜之间的融合在病毒进入中发挥核心作用。负责HIV-1病毒诱导的膜融合的蛋白(gp 41)长度不同,与S2没有序列同源性。序列分析表明,这两种病毒蛋白质共享的序列基序,构建其活性构象。这些包括(1)N-末端亮氨酸/异亮氨酸拉链样序列,和(2)位于(3)与(4)跨膜片段并置的富含芳香残基的区域上游的C-末端七肽重复序列。这项研究指出,两种病毒蛋白的作用模式相似,这表明可以采用针对病毒诱导的膜融合步骤的抗病毒策略,从HIV-1到SARS-CoV。最近,FDA批准恩夫韦肽作为抗艾滋病剂,恩夫韦肽是一种合成肽,对应于HIV-1 gp 41的C-末端七肽重复序列。恩夫韦肽和另一种抗HIV-1肽C34通过与gp 41中的亮氨酸/异亮氨酸拉链样序列结合,从而抑制gp 41活化所需的构象变化,从而发挥其抑制活性。我们认为,对应于S2蛋白的C-末端七肽重复序列的肽可以作为SARS-CoV进入的抑制剂。
Severe acute respiratory syndrome (SARS) is a febrile respiratory illness. The disease has been etiologically linked to a novel coronavirus that has been named the SARS-associated coronavirus (SARS-CoV), whose genome was recently sequenced. Since it is a member of the Coronaviridae, its spike protein (S2) is believed to play a central role in viral entry by facilitating fusion between the viral and host cell membranes. The protein responsible for viral-induced membrane fusion of HIV-1 (gp41) differs in length, and has no sequence homology with S2. Sequence analysis reveals that the two viral proteins share the sequence motifs that construct their active conformation. These include (1) an N-terminal leucine/isoleucine zipper-like sequence, and (2) a C-terminal heptad repeat located upstream of (3) an aromatic residue-rich region juxtaposed to the (4) transmembrane segment. This study points to a similar mode of action for the two viral proteins, suggesting that anti-viral strategy that targets the viral-induced membrane fusion step can be adopted from HIV-1 to SARS-CoV. Recently the FDA approved Enfuvirtide, a synthetic peptide corresponding to the C-terminal heptad repeat of HIV-1 gp41, as an anti-AIDS agent. Enfuvirtide and C34, another anti HIV-1 peptide, exert their inhibitory activity by binding to a leucine/isoleucine zipper-like sequence in gp41, thus inhibiting a conformational change of gp41 required for its activation. We suggest that peptides corresponding to the C-terminal heptad repeat of the S2 protein may serve as inhibitors for SARS-CoV entry.
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: 10.1073/pnas.95.26.15613
发表时间: 1998-12-22
影响因子: 11.1
作者:
Chan, DC;Chutkowski, CT;Kim, PS
通讯作者: Kim, PS
DOI: 10.1093/bioinformatics/17.9.849
发表时间: 2001-09-01
期刊: BIOINFORMATICS
影响因子: 5.8
作者:
Tusnády, GE;Simon, I
通讯作者: Simon, I
DOI: 10.1073/pnas.91.21.9770
发表时间: 1994-10-11
影响因子: 11.1
作者:
WILD, CT;SHUGARS, DC;MATTHEWS, TJ
通讯作者: MATTHEWS, TJ
DOI: 10.1038/71503
发表时间: 2000-01-01
期刊: NATURE MEDICINE
影响因子: 82.9
作者:
Pastey, MK;Gower, TL;Graham, BS
通讯作者: Graham, BS