Protease Inhibitors Could Act Against Avian Influenza

NEW YORK (Reuters Health) - HIV protease inhibitors (PIs) may be an effective treatment against avian influenza, according to results of computer modelling by an Italian researcher.

The H5N1 avian flu is considered a global health threat, with no effective treatment or vaccine in sight (see Reuters Health report, February 22, 2005).

Evidence that PIs may be of use against H5N1 is indirect, suggested by findings that these agents are effective against a third virus, the severe acute respiratory syndrome coronavirus which bears structural similarities to H5N1.

In a paper to be published in an upcoming issue of the Journal of Clinical Virology, Dr. Andrea Savarino of the Catholic University of the Sacred Heart, Rome, discusses how the anti-HIV drug Kaletra (a combination of PIs ritonavir and lopinavir) showed potential benefit in treating patients with the SARS.

This was surprising, since the SARS coronavirus does not encode an aspartic protease resembling that of the HIV virus. However, Dr. Savarino told Reuters Health, computational simulations showed that the main coronavirus protease 3C-like protease (3CL-pro) possesses a chymotrypsin-like folding against which PIs are effective.

He writes that "the possibility that PIs may dock to the active site of 3CL-pro is intriguing as it extends the potential effects of these drugs beyond those organisms possessing aspartic proteases resembling the HIV-1 protease."

His computer modeling revealed sequence similarity between the 3CL-pro chymotrypsin-like folding and that of the PA subunit of H5N1's putative protease component RNA-directed RNA polymerase (RdRp).

Thus "there is a steric compatibility between PIs and the influenza H5N1 PA subunit," Dr. Savarino added.

"The message I would like to give to the world," he concluded, "is that there is enough evidence to begin testing HIV PIs against the deadly H5N1 virus, both in vitro and in vivo."

Source: J Clin Virol 2005. [ Google search on this article ]

MeSH Headings: Computer Simulation : Computing Methodologies : Enzyme Inhibitors : Enzymes, Coenzymes, and Enzyme Inhibitors : Information Science : Medical Informatics : Medical Informatics Computing : Influenza A Virus, Avian : Protease Inhibitors : HIV Protease Inhibitors : Anti-HIV Agents : Chemical Actions and Uses : Chemical Actions : Chemicals and Drugs : Information Science