Viral chemotherapy

Hagiwara T, Kijima-Suda I, Ido T, Ohrui H, Tomita K (1994) Inhibition of bacterial and viral sialidases by 3-fluoro-V-acetyIneuraminic acid, Carbohydr Res 263 167-172 Haskell TH, Peterson FE, Watson D, Plessas NR, Culbertson T (1970) Neuraminidase inhibition and viral chemotherapy, J Med Chem 13 697-704 Hatakeyama S, Sugaya N, Ito M, Yamazaki M, Ichikawa M, Kimura K, Kiso M, Shimizu H, Kawakami C, Koike K, Mitamura K, Kawaoka Y (2007) Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors, JAMA 297 1435-1442 Hay AJ (1992) The action of adamantanamines against influenza A viruses inhibition of the M2 ion channel protein, Semin Virol 3 21-30... 

The effect of chemical and physical agents on viruses 9 The problems of viral chemotherapy... 

De Clercq E. Hamao Umezawa Memorial Award Lecture An odyssey in the viral chemotherapy field. Int J Antimicrob Agents 2001 18 309-328. 

Perrin DD, Stunzi Ei. Viral chemotherapy antiviral actions of metal ions and metal-chelating agents. Pharmac Ther 1981 12 255-297. 

Since viral disease constitutes such a large proportion of human illness, from the trivial incurable common cold to the so far totally deadly AIDS, a brief overview of the virus and its characteristics is essential to understand the unique problems encountered in viral chemotherapy and the apparently impossible obstacles to develop even specific antiviral... 

The obstacles to achieving rapid breakthrough results in viral chemotherapy are formidable. The main obstacles are complexity at the molecular/biochemical level, poor oral bioavailability (RO 31-8959, 4%), severe toxicities, and rapidly emerging resistance. This has been particularly disappointing with several of the nonnucleoside RT inhibitors. The HIV protease approach, improved RT inhibitors, or a combination of these and with cytokines, will hopefully improve AIDS therapy in this second decade of this worldwide pandemic. 

The immunorestorative potential of inosiplex has been evaluated in several clinical conditions, including post-surgical trauma, cancer patients with concurrent viral infections, and cancer patients receiving radiotherapy or chemotherapy. For example, most (84%) of the surgery patients remained immunologicaHy depressed, but 56% of the inosiplex-treated surgery patients had complete restoration of normal skin test reactivity (probability level < 0.0005). The use of inosiplex as an adjuvant to chemotherapy or radiotherapy appears to be valuable in the prophylaxis against opportunistic infections. 

Schinazi RF (1991) Combined therapeutic modalities for viral infections - rationale and clinical potential. In Chou TC, Rideout DC (eds) Synergism and antagonism in chemotherapy. Academic, Orlando, FL, pp 110-181... 

The human retrovirus HIV can be controlled using chemotherapy directed at the reverse transcriptase and aspartyl protease encoded by the viral genome as with other microbial pathogens, however, resistance to drug therapy becomes a major problem. Figure 7.3 shows a crystal structure (PDB 1HXW) of the HIV protease, where mutated amino acids (shown in cyan) lead to disrupted binding of the clinically effective inhibitor ritonavir [24]. 

Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan... 

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. 

Meunier, B., DNA and RATA Cleavers and Chemotherapy of Cancer or Viral Diseases, Kluwer Academic, 1996. 

Hairy cell leukemia Genital warts AIDS-related Kaposi s sarcoma Non-A non-B hepatitis Hepatitis B Malignant melanoma Chronic viral hepatitis C Follicular lymphoma with chemotherapy June 1986 June 1988 Nov. 1988 Feb. 1991 July 1992 Dec. 1995 March 1997 Nov. 1997... 

Currently, all donors and blood preparations undergo multistage and expensive control to ensure the absence of viral contamination In this respect, the development of affordable methods of inactivation of viruses could be an important step toward safety in hemotransfusion. Currently used treatments such as UV irradiation damage therapeutic components of the blood (Williamson and Cardigan, 2003), so alternative selective approaches are needed for this purpose. Among them, chemotherapy, photochemotherapy (PCT), and photodynamic antibacterial therapy should be noted (Mohr, 2000). 

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