Saquinavir

With a lot of bacterial strains becoming resistant to normal antibiotics, there has been a search for new antimicrobial drugs. Scientists began combining antimicrobial drugs for a synergistic effect, which made those drugs extremely effective. With the increase in technology, computers are now being used to design molecules. These molecules are being made to interact with specific microbial structures, and the most successful molecule made from a computer has been Saquinavir. Saquinavir is used in HIV therapy (antiviral), and it acts as an inhibitor for HIV protease. Protease is an enzyme that cleaves protein molecules into a bunch of smaller proteins. Stopping the protease stops HIV from virally replicating within an infected cell. The HIV protease contains catalytic aspartic acids that allow a catalytic cleavage reaction to occur (1). Saquinavir binds to the active site of HIV protease, and this binding keeps HIV dormant. It is very similar to the substrate that usually binds to the active site, but it is also different enough so it does not get cleaved by the aspartic acids. Saquinavir changes Glycine to Valine at position 48 in the HIV protease (1). It has been approved by the FDA and currently there are two formulations out on the market: Invirase and Fortovase. These drugs inhibit both HIV-1 protease and HIV-2 protease. When Saquinavir is taken with other low dose protease inhibitors (such as Ritonavir) its oral bioavailability is markedly increased (2). This allows for reduced dosing frequency and/or dosage. Some side effects of Saquinavir are diarrhea, nausea, vomiting, and tiredness.

References:
1. Perry, C.M, and S. Noble. "Saquinavir Soft-Gel Capsule Formulation: A Review of Its Use in Patients with HIV Infection." Drugs. N.p., 1998. Web. 21 Nov. 2013.
2. Figgitt, D.P., and G.L. Plosker. "Saquinavir Soft-Gel Capsule: An Updated Review of Its Use in the Management of HIV Infection." Drugs (2000): n. pag. Web. 21 Nov. 2013.