Infectious disease agents antivirals

Viruses are small infectious agents composed of a nucleic acid genome (DNA or RNA) encased by structural proteins and in some cases a lipid envelope. They are the causative agents of a number of human infectious diseases, the most important for public health today being acquired immunodeficiency syndrome (AIDS), hepatitis, influenza, measles, and vituses causing diarrhoea (e.g., rotavirus). In addition, certain viruses contribute to the development of cancer. Antiviral drugs inhibit viral replication by specifically targeting viral enzymes or functions and are used to treat specific virus-associated diseases. 

Viruses present a unique problem in terms of the pharmacologic treatment of infectious disease. These microorganisms rely totally on the metabolic function of host (human) cells to function and replicate more viruses. Hence, there are currently only a limited number of effective antiviral agents that selectively... 

The virus that causes smallpox. Variola major, is a Category A biological threat agent (CDC 2007). It is a double-stranded DNA orthopoxvirus. It is a widely held opinion among infectious disease professionals that, historically, smallpox has been responsible for more deaths than all other infectious diseases combined. After aggressive efforts by the World Health Organization to immunize the world s population, and because the virus is unable to survive for more than a week outside of its only host, humans. Variola was declared eradicated in 1980 (Murray et al. 2005). The smallpox vaccine can prevent or lessen the severity of the disease if administered within 96 h of exposure. The duration of effectiveness of the vaccine used to eradicate smallpox is not known, and there are reported mild to life-threatening risks are associated with the vaccine. Once a victim is symptomatic, medications and intravenous fluid can be administered to make the patient more comfortable, but there are no antivirals available for unvaccinated infected individuals (Henderson et al. 1999). 

Hayden FG. Update on antiviral agents and viral drug resistance. In Mandell GL, Douglas RGJ, Bennett JE, eds. Principles and Practice of Infectious Disease. New York Churchill Livingston, 1993 3-15. 

HDAC inhibitors are potentially useful for the treatment of infectious diseases. This is most well documented with the malaria parasite. Merck and GlaxoSmithKline have reported [17] a series of inhibitors based on the apicidin cyclic tetrapeptide natural product scaffold with some selectivity for Plasmodium over human HDACs. In the antiviral field, HDAC inhibitors were recently shown [18] to drive the expression of latent reservoirs of HIV, thus facilitating their eradication. Outside the human therapeutic areas, there is an interesting recent patent [19] by Dow who has independently isolated FK228, a HDAC inhibitor, from a Madagascar plant and shown that it is an antiinsecticidal agent. 

To determine if the high in vitro potents of the anti-HIV compound 30 translates into antiviral efficiency in vivo, Datema et al. investigated the inhibition of HIV-1 production and of depletion of human T cells in HIV-1-infected SCID-hu Thy/Liv mice [37]. Steady levels of 100 ng of 30 or higher per mL in plasma resulted in significant inhibition of HIV p24 protein formation. Daily injection of 30 caused a dose-dependent decrease in viral p24 production, and this inhibition could be potentiated by coadministration of AZT (or DDI). This study suggested that 30 alone or in combination with the licensed anti-HIV agents AZT and DDI may decrease the virus load in HIV-infected patients and, by extension, that the infectious cell entry step is a valid target for antiviral chemotherapy of HIV disease. 

Infectious virus diseases remain an important worldwide problem due to the nature of these infectious agents, which totally depend upon the cell that they infect for their multiplication and survival. This characteristic has made development of effective chemotherapeutic agents for treatment of viral infections very difficult, and as a consequence there are only a few antiviral drugs available for the cure of vims diseases. During the last years, the search for natural compounds with antiviral activity has been intensified. Antiviral screening programmes of indigenous medicinal plants are very important, not... 

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