Antiviral drugs essential

Abstract This review provides an overview of the development of viral protease inhibitors as antiviral drugs. We concentrate on HlV-1 protease inhibitors, as these have made the most significant advances in the recent past. Thus, we discuss the biochemistry of HlV-1 protease, inhibitor development, clinical use of inhibitors, and evolution of resistance. Since many different viruses encode essential proteases, it is possible to envision the development of a potent protease inhibitor for other viruses if the processing site sequence and the catalytic mechanism are known. At this time, interest in developing inhibitors is Umited to viruses that cause chronic disease, viruses that have the potential to cause large-scale epidemics, or viruses that are sufQciently ubiquitous that treating an acute infection would be... 

In the host cell, viruses induce the formation of enzymes that they themselves cannot produce. The most important group of such enzymes is that of the DNA polymerases, but thymidine kinase is also essential. Interference with these enzymes by either enzyme inhibitors or through fraudulent antimetabolites is the basis of the activity of many antiviral drugs. In this respect, antiviral compounds and cytostatics used in the treatment of malignant tumors have much in common and indeed overlap each other in their activity. 

As an example, we can consider the discovery and development of an antiviral drug. Inhibitors of the HIV protease, an enzyme essential for the maturation of the virus, can potentially cure HIV-infected people. The discovery process may consist of finding samples able to inhibit the viral aspartic protease over a certain threshold, while having little or no effect on another protease of the same class, such as pepsin. The hits will be submitted to further biological tests to identify leads, patentable compounds that are capable, for example, of inhibiting viral replication in cellular models. 

Reverse transcriptase is a key enzyme which plays an essential and multifunctional role in the replication of HIV-1 and thus constitutes an attractive target for the development of new drugs that could be used in AIDS therapy. A combination of reverse transcriptase and protease inhibitors is an effective approach to the treatment of AIDS [32], However, side effects and the clinical emergence of resistant mutants suggests an increasing need for novel antiviral drugs. 

Patients with VHF syndrome require close supervision, and some will require intensive care. Since the pathogenesis of VHF is not entirely understood and availability of specific antiviral drugs is limited, treatment is largely supportive. This care is essentially the same as the conventional care provided to patients with other causes of multisystem failure. The challenge is to provide this support while minimizing the risk of infection to other patients and medical personnel. 

Features of an ideal antiviral drug might include the following effective inhibition of an essential viral process, mechanism to prevent drug-resistant viruses from developing, broad-spectrum activity against RNA and DNA viruses, and no negative effect on host cell processes. 

Enyzme catalysis is thus essential for all life. Hence the selective inhibition of critical enzymes of infectious organisms (e.g., viruses, bacteria, and multicellular parasites) is an attractive means of chemotherapeutic intervention for infectious diseases. This strategy is well represented in modem medicine, with a significant portion of antiviral, antibiotic, and antiparasitic drugs in clinical use today deriving their therapeutic efficacy through selective enzyme inhibition (see Table 1.1 for some examples). 

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