Expanding the frontiers of existing antiviral drugs: possible effects of HIV-1 protease inhibitors against SARS and avian influenza.
When unexpected diseases such as the severe acute respiratory syndrome (SARS) and avian influenza become a serious threat to public health, an immediate response is imperative. This should take into consideration existing licensed antiviral drugs against other viral diseases already known to be safe for use in humans. In this report, evidence is presented that HIV-1 protease inhibitors (PIs) currently used in anti-HIV-1 therapies might exert some effects on SARS and perhaps, on avian influenza. Evidence for the potential benefits of PIs against the SARS coronavirus (SARS-CoV) is provided by empirical clinical studies, in vivo viral inhibition assays and computational simulations of the docking of these compounds to the active site of the main SARS-CoV protease. As suggested by in silico docking of these molecules to a theoretical model of a subunit of type A influenza virus RNA-dependent RNA polymerase, there also exists a remote possibility that these PIs may have an effect on avian influenza viruses. Although this evidence is still far from being definitive, the results so far obtained suggest that PIs should be seriously taken into consideration for further testing as potential therapeutic agents for SARS and avian influenza.
Savarino
Andrea
A
Laboratory of Viral Immunology, Department of Infectious Diseases, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, I-00168 Rome, Italy. asavarino@medscape.com
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001717:Birds; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D009980:Influenza A virus; D005585:Influenza in Birds / Q000188:drug therapy*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects; D016415:Sequence Alignment; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy*
D000998:Antiviral Agents; D017320:HIV Protease Inhibitors