Antiviral agents immunodeficiency virus

Rossmann, M.G. Antiviral agents targeted to interact with viral capsid proteins and a possible application to human immunodeficiency virus. Proc. Natl. Acad. Sci. USA, 85 4625-4627, 1988. 

In this chapter, we have described the spectrum of antiviral activities that have been discovered beyond the world of nucleoside analogues, protease and fusion inhibitors. The compounds and mechanisms described here may one day add significantly to the armamentarium of antiviral agents, not only against Herpes Simplex, Hepatitis B and Human Immunodeficiency Virus, but also against Hepatitis C and Human Cytomegalovirus. 

Dideoxyuridine (ddU) is an antiviral agent that proved ineffective at controlling human immunodeficiency virus type 1 (HIV-1) infection in human T-cells. This ineffectiveness was ascribed to a lack of substrate affinity of ddU for cellular nucleoside kinases, which prevent it from being metabolized to the active 5 -triphosphate. To overcome this problem, bis[(pivaloyloxy)methyl] 2, 3 -dideoxyuridine 5 -monophosphate (9.41) was prepared and shown to be a membrane-permeable prodrug of 2, 3 -di-deoxyuridine 5 -monophosphate (ddUMP, 9.42) [93]. Indeed, human T-cell lines exposed to 9.41 rapidly formed the mono-, di-, and triphosphate of ddU, and antiviral activity was observed. This example again documents... 

Hydrolysis of the diastereoisomerically pure Strecker product under racemization-free acidic conditions, followed by hydrogenolysis of the benzylic C-N bond, results in a 73% overall yield of (S)-tert-leucine (11). The amino acid 11 is an interesting, sterically constrained amino acid that is applied in various new antiviral and anti-HIV (human immunodeficiency virus) agents. 

Since 3 -azido-3 -deoxythymidine (AZT, Zidovudine, Retrovir) was identified by Mitsuya and co-workers as a potent antiviral agent against immunodeficiency virus type I (HIV-1), a number of other nucleosides have been found to inhibit HIV-I in vitro. The most important representatives are the 2, 3 -didcoxy nucleosides ddl, ddG, and ddA as well as their corresponding 2, 3 -didehydro derivatives. ... 

Dornsife RE, Averett DR. In vitro potency of inhibition by antiviral drugs of hematopoietic progenitor colony formation correlates with exposure at hemotoxic levels in human immunodeficiency virus-positive humans. Antimicrob Agents Chemother 1996 40(2) 514-19. 

The ability to prevent viral infections is becoming an increasingly important part of clinical medicine. The interest in the development of new antiviral agents and new uses of these medications is driven in large part by the treatment of human immunodeficiency virus (HIV) and growth of the field of transplantation. Although most of the use of these antiviral agents is well-tolerated by patients, there are a variety of potential kidney toxicities that should be appreciated. The most important of these toxicities is acute kidney injury (AKI), which is the main focus of... 

Larder, B. A., Chesebro, B., and Richman, D. D. (1990) Susceptibilities of zidovudine-susceptible and -resistant human immunodeficiency virus isolates to antiviral agents determined by using a quantitative plaque reduction assay. Antimicrob. Agents Chemother. 34,436 141. 

The trisodium salt of phosphonofonnic acid (PFA), called Foscamet, is an effective antiviral agent with potential application in acquired immunodeficiency syndrome (AIDS) therapy. PFA inhibits replication of HIV-I in the laboratory and reduces viremia in patients with AIDS. It also inhibits DNA polymerase from cytomcgalovims (CMV), herpes simplex virus (HSV), and other DNA vimses and thus has been useful in the treatment of secondary viral infections in AIDS patients. Because PFA bears a stmctural resemblance to pyrophosphate, it can be viewed as a product analogue as opposed to a substrate analogue. 

Erice, A., Balfour, H. H., Jr., Myers, D. E., Leske, V. L., Sannerud, K. J., Kuebelbeck, V., Irvin, J. D., and Uckun, F. M. (1993) Anti-human immunodeficiency virus type 1 activity of an anti-CD4 immunoconjugate containing pokeweeci antiviral protein. Antimicrob. Agents Chemother. 37, 835-338. 

The number of available antiviral agents has increased dramatically over the last five years, especially with the introduction of many new agents used primarily to treat human immunodeficiency virus (HIV) infection. Fortunately, most antiviral agents do not cause acute or chronic renal failure, glomerular disease, or other renal toxicity. Acute renal failure is, however, an important and potentially therapy-limiting toxicity of some antiviral agents, which are the main focus of this chapter. In this chapter, we have adopted... 

Evidence of antiviral effects has especially been shown for St. John s Wort [2,3,10], Plant preparations with different chemical composition have been assayed against various viruses and both, hypericin and pseudohypericin, were found to be particularly effective as virucidal agents. The two compounds have been shown to be active against a broad range of viruses and retroviruses, such as herpes simplex virus types I and II, vesicular stomatitis and influenza viruses, cytomegalovyrus and human immunodeficiency virus-1 [2,3,10,91,92]. 

Poppe SM, Slade DE, Chong K-T, et al. Antiviral activity of the dihydropyrone PNU-140690, a new nonpeptidic human immunodeficiency virus protease inhibitor. Antimicrob Agents Chemother 1997 41 1058-1063. 

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