Anti-viral treatments

Russian scientists may have continued work on this virus. This includes the introduction of Ebola and VEE genes into smallpox to create a whole new kind of BW agent, a so-called chimera virus. This would not only resist vaccine or anti-viral treatments, but also have a synergistic effect. In the late 1980s, a strain of a combined ectromelia (mousepox, a close relative of smallpox) and VEE genes created symptoms of both diseases in laboratory animals. Ken Alibek is convinced that this BW-related research work still continues in Russia, despite Yeltsin s decree banning all such activity. ... 

Obviously the best treatment for cirrhosis is removal of the injurious event. In the case of viral hepatitis, viral load can at least be temporarily reduced with anti-viral agents such as lamivudine, ribavirin and/or IFNa [76]. Unfortunately, complete removal of the injurious event is frequently not possible. Moreover, by the time cirrhosis is diagnosed the fibrotic process has usually progressed beyond the point of no return and removal of the injurious event will have little effect. Successful pharmacological treatment to reverse the fibrotic... 

Viruses are obligate intracellular organisms as their replication is based on DNA and RNA dependent processes and protein synthesis of the host. Antiviral therapy can therefore not be as selective as antibacterial treatments and anti-viral agents tend to inhibit host cell function and can cause major toxicity. An other problem with antiviral therapy is the fact that active viral replication mostly takes place before symptoms become manifest. Our armamentarium against most viral infections is limited. 

Trifluoromethyl-2 -deoxyuridine, trifluridine (Viroptic ), is an anti-viral drug acting on TS via another mechanism. It is a mechanism-based inactivator of thy-midylate synthase (Figs. 27 and 28). Trifluridine is marketed for the topical treatment of Herpes simplex virus infection in eyes. 

Ribozymes have been applied as anti-viral agents, for the treatment of cancer and genetic disorders, and as tools for pathway elucidation and target validation. Initial uses of ribozymes focused on anti-viral, primarily for the treatment of HIV (Rossi, 1999). Viruses that go through a genomic RNA intermediate in their replication cycle, such as HIV, hepatitis B virus and hepatitis C vims are attractive targets because a single... 

Smales CM, Pepper DS, James DC (2002), Protein modification during anti-viral heat-treatment bioprocessing of factor VIII concentrates, factor IX concentrates, and model proteins in the presence of sucrose, Biotechnol. Bioeng. 77 37-48. 

The enzymes that manipulate nucleotides, nucleic acids, etc. are the points of therapeutic intervention for a number of diseases involving cell replication disorders such as cancers and viral infections. For instance, AZT 10.10, an inhibitor of the enzyme reverse transcriptase, is an anti-viral drug currently used in the treatment of AIDS. 

Proteins are also used clinically to treat a variety of diseases. Erythropoietin stimulates erythrocyte production in kidney dialysis and chemotherapy patients. Granulocyte stimulating factor enhances immune systems compromised by cancer treatments. Cytokines such as interferons and interleukins are used for their anti-viral and anti-tumor activities. Other proteins are used to inhibit or stimulate blood clotting. For the most part, the pharmaceutical protein industry relies on cloning native human genes and expressing and purifying their products in recombinant form. 

The only division in CDER with an established policy regarding pre-IND consultation meetings is the Division of Anti-Viral Drug Products (DAVDP). Established in 1988, the DAVDP pre-IND Consultation Program is a proactive strategy designed to facilitate informal early communications between DAVDP and potential sponsors of new therapeutics for the treatment of AIDS and life-threatening opportunistic infections, other viral infections, and soft tissue trans-... 

An example of the use of a terpene as a chiral auxiliary is provided by the synthesis of the anti-viral reverse transcriptase inhibitor Lamivudine (148). The nucleoside analog is marketed by Biochem Pharma (now Shire Pharmaceuticals) and Glaxo Wellcome (now GlaxoSmithKline) for the treatment of HIV and hepatitis B virus infection. In the... 

Multiple Sclerosis is a disease of unknown etiology or therapy. The article brought up the other day in the newspaper stating that there may have been established a viral etiology for multiple sclerosis should not be too surprising, in as much as that has been the concept for the past 20 or 30 years. To undertake a treatment using oxidative therapy should not otherwise be too unusual, since oxidative therapy is known to be anti-viral. 

Mycophenolic acid has anti-fungal, anti-bacterial and anti-viral activity. It is a potent inhibitor of inositol monophosphate dehydrogenase and guanosine monophosphate synthase and hence of nucleotide biosynthesis. Mycophenolic acid has a powerful immunosuppressive activity and the morpholine amide (CellCept ) is used to prevent rejection of organ transplants and has been recommended for the treatment of psoriasis. 

One synthesis of the important anti-viral drug AZT 163 (Azidothymidine, used in the treatment of HIV) shows this. The doubly silylated thymine 161 combines with the azido-sugar 162 under Lewis acid catalysis to give AZT after work-up. Only 33% of the required diastereoisomer 163 can be isolated and about the same amount of the other is formed.18... 

The rest of this chapter will show how the most successful treatment modalities have developed. These include vaccination (for smallpox, polio, measles, etc.), and chemotherapy using anti-viral drugs. A large number of viral diseases still lack an effective means of treatment, and the chapter will also cover the attempts to treat the common cold and influenza the struggles with HIV and the emergence of viruses (Marburg, Ebola, Lassa) that cause haemorrhagic fever. 

Zanamivir (8)is an inhaled anti-viral drug for the treatment of uncomplicated types A and B influenza, the two types most responsible for flu epidemics (14). Patients need to start treatment within 2 days of the onset of symptoms, and the drug is less effective in patients whose symptoms do not include a fever. Zanamivir (8)is a powder that is inhaled twice... 

In contrast to zanamivir (8), oseltamivir (9) is an oral anti-viral drug for the treatment cf uncomplicated influenza in patients whose flu symptoms have not lasted more than 2 days (15, 16). This product treats types A and B influenza however, the majority of patients in the United States are infected with type A. FTTit ay of oseltamivir (9) in the treatment of influenza in subjects with chronic cardiac disease and/or respiratory disease has not been established. Oseltamivir (9) is also approved for the prevention of influenza in adults and adolescents older than 13 years. Efficacy of oseltamivir (9) for the prevention of influenza has not been established in immune-compromisedpatients. 

We will discuss small molecule inhibitors of three main classes of nonprotein kinases sugar kinases, nucleoside kinases and lipid kinases. This chapter will be limited to discussion of the inhibition of human kinases. Several non-human non-protein kinases have been the focus of drug development efforts as well, including choline kinase for inhibition of Plasmodium, uridine-cytidine kinase as an anti-parasitic target and thymidine kinase inhibitors as an anti-mycobacterial treatment or for treatment of Herpes simplex viral infections. These applications will not be discussed in this chapter. Peptide... 

Smales C M, Pepper D S, James D C (2000a). Mechanisms of protein modification during model anti-viral heat-treatment bioprocessing of P-Iactoglobulin variant A in the presence of sucrose. Biotechnol. Appl. Biochem. 32 109-119. 

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