Influenza is a disease known to continue to afflict a large number f people and cause many deaths throughout the world. Influenza A and B are the two types of influenza that cause epidemic human disease. The influenza illness is characterized by the abrupt onset of fever, myalgia, headache, and sore throat. Amantadine and rimantadine have been used to treatment and prophylaxis of influenza, but these agents can only reduce symptomatic illness due to influenza A virus and are ineffective against influenza B virus. Inhibitors of influenza neuraminidase constitute a new class of anti-influenza agents that reduce replication of influenza A and influenza B. Vaccination against influenza virus is the primary strategy to reduce the morbidity and mortality associated with influenza.
Amantadine ; Fever ; Headache ; Humans ; Influenza A virus ; Influenza B virus ; Influenza, Human* ; Mortality ; Myalgia ; Neuraminidase ; Orthomyxoviridae ; Pharyngitis ; Rimantadine ; Vaccination

Adamantane ; therapeutic use ; Amantadine ; therapeutic use ; Antiviral Agents ; therapeutic use ; Child ; Guanidines ; Humans ; Influenza, Human ; drug therapy ; prevention & control ; Pyrans ; Rimantadine ; therapeutic use ; Sialic Acids ; therapeutic use ; Zanamivir

The M2 proteins of influenza A and B virus, AM2 and BM2, respectively, are transmembrane proteins that oligomerize in the viral membrane to form proton-selective channels. Proton conductance of the M2 proteins is required for viral replication; it is believed to equilibrate pH across the viral membrane during cell entry and across the trans-Golgi membrane of infected cells during viral maturation. In addition to the role of M2 in proton conductance, recent mutagenesis and structural studies suggest that the cytoplasmic domains of the M2 proteins also play a role in recruiting the matrix proteins to the cell surface during virus budding. As viral ion channels of minimalist architecture, the membrane-embedded channel domain of M2 has been a model system for investigating the mechanism of proton conduction. Moreover, as a proven drug target for the treatment of influenza A infection, M2 has been the subject of intense research for developing new anti-flu therapeutics. AM2 is the target of two anti-influenza A drugs, amantadine and rimantadine, both belonging to the adamantane class of compounds. However, resistance of influenza A to adamantane is now widespread due to mutations in the channel domain of AM2. This review summarizes the structure and function of both AM2 and BM2 channels, the mechanism of drug inhibition and drug resistance of AM2, as well as the development of new M2 inhibitors as potential anti-flu drugs.
Amantadine ; pharmacology ; Antiviral Agents ; pharmacology ; Drug Resistance, Viral ; genetics ; Genes, Viral ; Humans ; Influenza A virus ; chemistry ; drug effects ; genetics ; Influenza B virus ; chemistry ; drug effects ; genetics ; Ion Channels ; chemistry ; drug effects ; genetics ; Models, Molecular ; Mutation ; Protein Structure, Tertiary ; Rimantadine ; pharmacology ; Viral Matrix Proteins ; chemistry ; drug effects ; genetics ; Viral Proteins ; chemistry ; drug effects ; genetics

Influenza is a major threat to millions of people worldwide. Vaccines and antiviral agents are two main options available to reduce the impact of the influenza virus, while anti-influenza agents are the most effective means to prevent the transmission of the highly contagious virus and to treat the epidemics of disease. At present, four anti-influenza agents have been approved by the FDA for the treatment of influenza, including two M2 protein ion channel inhibitors-amantadine and rimantadine and two neuraminidase inhibitors-zanamivir and oseltamivir. Arbidol hydrochloride, launched in Russia, is a potent inhibitor of influenza virus, too. Neuraminidase inhibitors could be classified generally by structure into six different kinds: sialic acid derivatives, benzoic acid derivatives, cyclohexene derivatives, cyclopentane derivatives, pyrrolidine derivatives and natural products. In this paper, recent progress in the research of the action mechanisms and structure-activity relationships of these anti-influenza virus agents were reviewed.
Amantadine ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Antiviral Agents ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Cyclopentanes ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Guanidines ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Humans ; Indoles ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Influenza, Human ; drug therapy ; Neuraminidase ; antagonists & inhibitors ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Orthomyxoviridae ; drug effects ; Oseltamivir ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Pyrrolidines ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Rimantadine ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Structure-Activity Relationship ; Viral Matrix Proteins ; antagonists & inhibitors ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Zanamivir ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use