Development of Antivirals for Influenza

Influenza viruses, a class of single-stranded RNA virus, continue to cause serious respiratory disethe world. Type A influenza virus causes pneumonia and deaths, especially in the elderly. Type B infinfect a younger population than does Type A and are associated with Reye's syndrome. With antigenicinfluenza viruses are capable of producing disease in people of all ages. The only effective antiviramantadine and its close relative rimantadine. Although these drugs can be quite effective against ionly against disease caused by Type A influenza virus and are not well-tolerated in the elderly groumorbidity and mortality. Considerable morbidity and mortality also occur with Type B influenza. Receresistant to amantadine have been identified. Use of other reagents (e.g., ribavirin and interferon)side effects. Hence, there is a great need of new antiviral drugs for influenza. Our long-term goalspectrum antiviral agent against influenza that can inhibit the replication of both influenza A andbased on the virus transcription inhibitory properties of influenza matrix protein (M1). A syntheticfragment (Peptide 6) of M1 has been identified which inhibits influenza RNA polymerase leading to intranscription (IC50=0.5nM). Recently, the applicant demonstrated that Peptide 6 inhibits cytopathicinfluenza virus on MDCK cell monolayers. This peptide has a great potential as an antiviral agent foapplication entitled "M-Protein Peptides of Influenza Virus As Antiviral Agents" was filed on June 1during Phase I is to conduct feasibility studies on Peptide 6 for its in vivo influenza virus inhibidetermination will be made whether it is feasible to shorten the length of Peptide 6 and to determinrequired for in vitro CPE inhibitory effect. Phase II studies will involve the synthesis of a metabocandidate peptide will be tested against different strains of type A and type B influenza viruses. Ttest the effect of the peptide on normal cellular functions. Pharmacokinetics, cell penetration, andbe conducted. An inhalation delivery device will be developed.