H5N1 influenza virus

As a result of the emergence of the extremely aggressive avian H5N1 influenza virus, the likelihood of a human influenza pandemic and the possible socioeconomic impact is now of major concern. In the absence of strain-independent anti-influenza drugs, there has been significant effort worldwide over the years in the quest for the discovery of novel therapeutic agents against all types of influenza. 

Fortunately, more biologists are becoming aware of the dangers, one virologist warning that [t]here is every reason to believe that the. .. recombinant DNA techniques can be used to render this H5N1 [influenza] virus transmissible from humans to humans 17 and thus create a deadly new epidemic. 

Stevens,J., O. Blixt, T. Tumpey,J. Taubenberger, J. Paulson, and I. Wilson. Structure and Receptor Specificity of the Hemagglutinin from an H5N1 Influenza Virus. Science % i, 404-410... 

Stevens J, Blixt O, Tumpey TM, Taubenberger JK, Paulson JC, Wilson lA. Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus. Science 2006 312 404-410. 

An interesting feature of the influenza virus sialidase active site that offers the potential for developing inhibitors specific for N1 sialidases, including avian influenza A/H5N1 virus sialidase, has recently been revealed by X-ray crystallography. The... 

Chong AK, Pegg MS, Taylor NR, von Itzstein M (1992) Evidence for a sialosyl cation transition-state complex in the reaction of sialidase from influenza virus. Eur J Biochem 207 335-343 Cinatl J Jr, Michaelis M, Doerr HW (2007a) The threat of avian influenza A (H5N1). III. Antiviral therapy. Med Microbiol Immunol 196 203-212... 

Hurt AC, lanneUo P, Jachno K, Komadina N, Hampson AW, Barr IG, McKimm-Breschkin JL (2006) Neuraminidase inhibitor-resistant and -sensitive influenza B viruses isolated from an untreated human patient, Antimicrob Agents Chemother 50 1872-1874 Hurt AC, Selleck P, Komadina N, Shaw R, Brown L, Barr IG (2007) Susceptibility of highly pathogenic A(H5N1) avian influenza viruses to the neuraminidase inhibitors and adamantanes. Antiviral Res 73 228-231... 

Examples of killed or inactivated vaccines are cholera vaccine containing dead strains of Vibrio cholerae, hepatitis A vaccine with inactivated hepatitis A virus, pertussis vaccine with killed strains of Bordetella pertussis, typhoid vaccine with killed Salmonella typhi, and influenza vaccine with various strains of inactivated influenza viruses (see Exhibit 4.2 for a discussion of influenza viruses and vaccines and Exhibit 4.3 on avian influenza H5N1). 

Currently, two classes of drugs are available with antiviral activity against influenza viruses inhibitors of the ion channel activity of the M2 membrane protein, amantadine and rimantadine, and the neuraminidase inhibitors oseltamivir, and zanamivir. H5N1 viruses isolated from poultry and humans in Thailand and Viet Nam in 2004 invariably showed an amantadine-resistance indicating that amantadine treatment is not an option during the ongoing outb-treak in South-East Asia. 

The worldwide spread of H5N1 avian influenza virus has raised the concern of its potential to emerge as a human-adapted virus. Three decades of intense research have yielded only two NA inhibitors, Relenza and Tamiflu , that... 

Since 1997, avian influenza (H5N1) has been an emerging public health threat. The first confirmed human death from avian influenza was a 3-year-old with Reye s syndrome (Lee Krilov, 2005). From 1997 through 2002, only a handful of people died, including children. In 2003 and onward, the death rate from avian influenza has increased dramatically. At this time, avian influenza is transmitted from direct contact with infected fowl. Current public health concerns are the mutation of the influenza virus into one that transmits from human to human. Thai and Vietnamese children... 

Therapies for typical human influenza viruses should work in treating avian influenza infection in humans however, influenza viruses can become resistant to drugs such as amantadine and rimantadine, decreasing their effectiveness. Currently no vaccine is available to protect humans against the H5N1 virus that causes... 

---