DRUG DESIGN

The Concept of Drug Design

The Concept of Drug Design

HIV/AIDS Protease Inhibitor

As HIV disease progresses, drug treatment may be implemented, if available and affordable. Antiviral drugs work by interrupting the processes required for the virus to enter the cell and to use the cell to replicate. There are several different types of antiviral medications used to treat HIV disease (DiClemente, 2007). Protease inhibitors interrupt the replication cycle of the virus at a later stage in its life cycle. Specifically, these drugs interfere with the protease enzyme that HIV uses to produce infectious viral particles.

Protease inhibitors interfere with HIV replication by inhibiting the enzyme protease and the process of cutting proteins to the appropriate length for creation of new HIV. Drugs designed to inhibit the integrase enzyme and to block the attachment of HIV to the fusin protein are in development. However, current HIV treatment uses a combination of drugs to inhibit viral replication.

This approach, combination therapy, cocktail therapy, or more specifically, highly active antiretroviral treatment (HAART), uses drugs of different types. For example, a common combination includes two reverse transcriptase inhibitors and one protease inhibitor. This treatment has been found to reduce viral load below detectable levels in many patients (DiClemente, 2007).

HIV protease inhibitors

HIV protease inhibitors also interrupt the replication stage of the virus, but does so at a later stage during the process (DiClemente, 2007).

Several other reverse transcriptase inhibitors were developed in the 1990s, but it was not until 1995 that a significantly new type of antiviral medication was approved by the FDA. In 1995, the protease inhibitor saquinavir mesylate, marketed as Invirase, was approved. Subsequently, other protease inhibitors have been developed and approved. Currently, HAART involves multiple medications, usually two reverse transcriptase inhibitors and one protease inhibitor. Combination therapies were approved in 2000, which showed significant effects at reducing viral load, morbidity (i.e., illness), and mortality. In fact, AIDS mortality in the United States dropped by about 50% with the development of HAART. With future developments of fusin blockers and integrase inhibitors, it may be expected that combination therapies may become even more effective.

Protease inhibitors (e.g., Invirase, Viracept, Norvir) prevent T-cells that have been infected with HIV from producing new copies of the virus by interrupting replication through binding and blocking the enzyme. HIV protease nRTIs (e.g., Retrovir, Epivir, Combivir) are incorporated into the DNA of the virus and stop the building process, resulting in incomplete DNA that cannot create a new virus. nnRTIs (e.g., Viramune, Rescriptor, Efavirenz) are designed to work at the final stage of the HIV replication process by preventing HIV protease from developing into HIV.

In combination, these drugs work to prolong the suppression of HIV replication, resulting in decreases in viral load to lower and in some cases even to undetectable levels in the blood. As a result, immune system cells such as CD4 + may increase in number, thus strengthening the immune system. More recently, two other classes of drugs have been developed— nucleotide reverse transcriptase inhibitors and fusion ...