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

Kliger Y, Levanon EY - BMC Microbiol. (2003)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Compugen LTD, Tel Aviv, 69512, Israel. kliger@compugen.co.il

ABSTRACT

Background: 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.

Results: 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.

Conclusions: 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.

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Sequence comparison of the aromatic residue-rich regions of HIV-1 gp41 and SARS-CoV S2 proteins. The aromatic residues are in blue. Remarkably, the relatively rare aromatic residues comprise about half of the residues in these region.
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Figure 4: Sequence comparison of the aromatic residue-rich regions of HIV-1 gp41 and SARS-CoV S2 proteins. The aromatic residues are in blue. Remarkably, the relatively rare aromatic residues comprise about half of the residues in these region.

Mentions: Markedly, LearnCoil-VMF [17], helical wheel analysis and protein topology prediction [18] reveal that the SARS-CoV S2 protein consists of the same elements that were characterized in HIV-1 gp41 (Figure 2b): (I) N-HR, a Leucine/Isoleucine heptad repeat appears on residues 913–1000 of the SARS-CoV CUHK-W1 isolate (Figure 3a).; (II) C-HR, a Leucine/Isoleucine heptad repeat appears on residues 1151–1185 (Figure 3b); (III) the loop between these two HRs is longer than that of gp41, and is confined by four Cysteine residues and nine Proline residues that might conform a double loop structure; (IV) a transmembrane region is predicted adjacent to the C-terminus of the protein [18]; (V) a Tryptophan/Tyrosine-rich motif is located between the C-HR and the transmembrane domain (Figure 4). The results reveal similar structural motifs in HIV-1 gp41 and SARS-CoV S2 proteins, suggesting an analogous membrane fusion mechanism induced by the two viruses.


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

Kliger Y, Levanon EY - BMC Microbiol. (2003)

Sequence comparison of the aromatic residue-rich regions of HIV-1 gp41 and SARS-CoV S2 proteins. The aromatic residues are in blue. Remarkably, the relatively rare aromatic residues comprise about half of the residues in these region.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC222911&req=5

Figure 4: Sequence comparison of the aromatic residue-rich regions of HIV-1 gp41 and SARS-CoV S2 proteins. The aromatic residues are in blue. Remarkably, the relatively rare aromatic residues comprise about half of the residues in these region.
Mentions: Markedly, LearnCoil-VMF [17], helical wheel analysis and protein topology prediction [18] reveal that the SARS-CoV S2 protein consists of the same elements that were characterized in HIV-1 gp41 (Figure 2b): (I) N-HR, a Leucine/Isoleucine heptad repeat appears on residues 913–1000 of the SARS-CoV CUHK-W1 isolate (Figure 3a).; (II) C-HR, a Leucine/Isoleucine heptad repeat appears on residues 1151–1185 (Figure 3b); (III) the loop between these two HRs is longer than that of gp41, and is confined by four Cysteine residues and nine Proline residues that might conform a double loop structure; (IV) a transmembrane region is predicted adjacent to the C-terminus of the protein [18]; (V) a Tryptophan/Tyrosine-rich motif is located between the C-HR and the transmembrane domain (Figure 4). The results reveal similar structural motifs in HIV-1 gp41 and SARS-CoV S2 proteins, suggesting an analogous membrane fusion mechanism induced by the two viruses.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Compugen LTD, Tel Aviv, 69512, Israel. kliger@compugen.co.il

ABSTRACT

Background: 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.

Results: 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.

Conclusions: 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.

Show MeSH
Related in: MedlinePlus