Cloaked similarity between HIV-1 and SARS-CoV suggests an anti-SARS strategy.
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.
D019380:Anti-HIV Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D015195:Drug Design; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology; D015497:HIV-1 / Q000737:chemistry* / Q000187:drug effects; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D011487:Protein Conformation; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry* / Q000187:drug effects; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D014760:Viral Fusion Proteins; C407149:peptide C34; D000077560:Enfuvirtide