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

BMC Microbiol. 2003 Sep 21;3:20. doi: 10.1186/1471-2180-3-20.

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.

MeSH terms

  • Anti-HIV Agents / pharmacology
  • Antiviral Agents / pharmacology
  • Drug Design
  • Enfuvirtide
  • HIV Envelope Protein gp41 / pharmacology
  • HIV-1 / chemistry*
  • HIV-1 / drug effects
  • Molecular Sequence Data
  • Peptide Fragments / pharmacology
  • Protein Conformation
  • SARS Virus / chemistry*
  • SARS Virus / drug effects
  • Viral Fusion Proteins / chemistry*
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / metabolism

Substances

  • Anti-HIV Agents
  • Antiviral Agents
  • HIV Envelope Protein gp41
  • Peptide Fragments
  • Viral Fusion Proteins
  • peptide C34
  • Enfuvirtide

Associated data

  • RefSeq/NC_004718