Developing new antiviral agents for influenza treatment: what does the future hold?
Antiviral agents for the treatment of influenza are urgently needed to circumvent the limitations of current drugs in several critical areas: high frequencies of resistance to M2 inhibitors among currently circulating strains and variable frequencies of resistance to oseltamivir among A(H1N1) strains, limited efficacy of treatment and treatment-emergent antiviral resistance in cases of avian influenza A(H5N1) illness in humans, and lack of parenteral agents for seriously ill patients. Two neuraminidase inhibitors (NAIs), zanamivir and peramivir, have undergone or are undergoing clinical trials for use by intravenous or intramuscular administration, and one long-acting NAI, designated CS-8958, is under study for use by inhalation. Advances in understanding the mechanisms involved in influenza virus replication have revealed a number of potential targets that might be exploited in the development of new agents. Among these agents are T-705, a polymerase inhibitor, and DAS181, an attachment inhibitor. Combination therapy with currently available agents is supported by data from animal models but has received limited clinical study to date.
Hayden
Frederick
F
Global Influenza Programme, World Health Organization, Geneva, Switzerland. fgh@virginia.edu
D000146:Acids, Carbocyclic; D000577:Amides / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003517:Cyclopentanes / Q000494:pharmacology / Q000627:therapeutic use; D055808:Drug Discovery / Q000639:trends*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects; D007251:Influenza, Human / Q000188:drug therapy*; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D011719:Pyrazines / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D053243:Zanamivir / Q000494:pharmacology / Q000627:therapeutic use
D000146:Acids, Carbocyclic; D000577:Amides; D000998:Antiviral Agents; D003517:Cyclopentanes; D006146:Guanidines; D011719:Pyrazines; D011993:Recombinant Fusion Proteins; C525612:oplunofusp; D009439:Neuraminidase; C462182:favipiravir; D053243:Zanamivir; C414210:peramivir