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

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.Infection by many enveloped viruses requires fusion of the viral and cellular membranes. A viral envelope protein mediates this membrane fusion process. These proteins are synthesized as precursors (ENV in Retroviridae, and E2 in Coronaviridae) that are later processed into a transmembrane subunit (gp41 in the retrovirus HIV-1, and S2 in the coronavirus SARS-CoV) that is responsible for viral-induced membrane fusion, and a surface subunit that is responsible for the interaction with the cellular receptor/s.HIV-1 gp41, which is a well-characterized protein [1,2] contains two heptad repeat (HR) regions, a leucine/isoleucine HR adjacent to its N-terminus (N-HR), and C-HR proximal to the transmembrane domain (see Figure 1). Heptad repeats are characterized by hydrophobic amino acids in the "a" and "d" positions of the helix. In the N-HR of gp41, all but one of the "a" positions are Leucines or Isoleucines. This feature is less strict in the "d" positions of N-H