Human immunodeficiency virus specific agents

Balzarini J, Schols D, Neyts J, Van Damme E, Penmans W, De Clercq E. a-(1-3)- and a-(l-6)-d-mannose-specific plant lectins are markedly inhibitory to human immunodeficiency virus and cytomegalovirus infections in vitro. Antimicrob Agents Chemother 1991 35 410-416. 

Replication of the human immunodeficiency virus (mV), the causative agent of AIDS, is susceptible to targeted interventions, because several virus-specific metabolic steps occur in infected cells (A). Viral RNA must first be transcribed into DNA, a step catalyzed by viral reverse transcriptase." Double-stranded DNA is incorporated into the host genome with the help of viral inte-grase. Under control by viral DNA, viral replication can then be initiated, with synthesis of viral RNA and proteins (including enzymes such as reverse transcriptase and integrase, and structural proteins such as the matrix protein lining the inside of the viral envelope). 

The viral protease enzyme, human immunodeficiency virus type 1 (HIV-1), is a causative agent of AIDS. HIV-1 mediates the processing of the viral precursor polyproteins. This process is essential for the production and maturation of infectious viruses [1,2]. CR1XIVAN is a specific and potent inhibitor of the HIV-1 protease, and is used in the treatment of AIDS. 

Boyer PL, Ding J, Arnold E, Hughes SH. Drug resistance of human immunodeficiency virus type 1 reverse transcriptase subunit specificity of mutations that confer resistance to nonnucleoside inhibitors. Antimicrob Agents Chemother 1994 38 1909-1914. 

Another therapeutic application of polyhydroxylated alkaloids is as anti-viral agents. Inhibitors of processing a-glucosidases, such as castanospermine and DNJ, have been shown to decrease the infectivity of human immunodeficiency virus (HIV) in vitro at concentrations which are not cytotoxic to lymphocytes, whereas specific inhibitors of processing a-mannosidases (swainsonine and 1-deoxymannojirimycin) have no effect on Castanospermine and DNJ also reduce the infectivity of other retroviruses... 

A key strategy in the treatment of acquired immunodeficiency syndrome (AIDS) has been to develop specific inhibitors that selectively block the actions of enzymes unique to the human immunodeficiency virus (HIV), which causes AIDS. Many laboratories are working on this approach to the development of therapeutic agents. Three key enzymes are current targets for AIDS therapy—reverse transcriptase, integrase, and protease. 

Balzarini, J. Schols, D. Neyts, J. Van Damme, E. Peumans, W. De Clercq, E. a-(l-3)-D- Mannose-Specific Plant Lectins Are Markedly Inhibitory to Human Immunodeficiency Virus and Cytomegalovirus Infections In Vitro. Antimicrob. Agents Chemother. 1991, 35, 410-416. 

Hizi, A. Tal, R. Shaharabary, M. Currens, M.J. Boyd, M.R. Hughes, S.H. McMahon, J.B. Specific Inhibition of The Reverse Transcriptase of Human Immunodeficiency Virus Type 1 and The Chimeric Enzymes of Human Immunodeficiency Virus Type 1 and 2 by Non- nucleoside Inhibitors. Antimicrob. Agents Chemother. 1993,57, 1037-1042. 

Within 1-3 years after the discovery of human immunodeficiency virus (HIV) as the causative agent of acquired immune deficiency syndrome (AIDS) (1,2), the CD4 molecule was identified as the primary HIV receptor (3). HIV was shown to enter target cells by an initial binding event between the envelope glycoprotein (Env) molecules on the viral membrane and CD4 molecules on the target cell surface, followed by direct, pH-independent membrane fusion. Yet as early as 1986, it became clear that the Env-CD4 interaction was not sufficient to promote the fusion reaction (4-6) several lines of evidence indicated that the target cell must contain an additional human-specific cofactor (7-11), presumably a coreceptor. ... 

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. 

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