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Nelfinavir, better known as Viracept, (1ohr)
Better Known as: Viracept
- Marketed By: Agouron Pharmaceuticals (now part of Pfizer) & Roche
- Major Indication: Human Immunodeficiency Virus Infection
- Drug Class: HIV Protease Inhibitor
- Date of FDA Approval (Patent Expiration): 1997 (2014)
- 2004 Sales: $400 Million
- Importance: Soon after its approval, it became the vest selling HIV Protease inhibitor monotherapy in the world.
- See Pharmaceutical Drugs for more information about other drugs and disorders.
Mechanism of Action
When HIV infects a host, it directs the synthesis of several polyproteins during its maturation process. The maturation of the virus to its infectious form requires that these polyproteins be cleaved to their component proteins by HIV Protease. The two subunits of come together to form a catalytic tunnel capable of binding the nascent peptides and cleaving them into their mature form. Buried within this tunnel lies , which contain the . These catalytic Asp residues carry out the hydrolytic cleavage of the viral polyproteins. Nelfinavir to these conserved sequences within the HIV Protease tunnel, preventing the nascent polyproteins from entering. Unable to actively cleave the nascent proteins into their functional form, HIV is unable to mature and proliferate, allowing the patients immune system to fight off the infection more easily.
The biggest difficulty with treating HIV is the rapidity at which it mutates and becomes resistant to treatments. To view a comprehensive and interactive analysis of the mutations which confer drug resistance to HIV Protease, See: HIV Protease Inhibitor Resistance Profile
For Pharmacokinetic Data References, See: References
- ↑ Spinelli S, Liu QZ, Alzari PM, Hirel PH, Poljak RJ. The three-dimensional structure of the aspartyl protease from the HIV-1 isolate BRU. Biochimie. 1991 Nov;73(11):1391-6. PMID:1799632
- ↑ Tie Y, Kovalevsky AY, Boross P, Wang YF, Ghosh AK, Tozser J, Harrison RW, Weber IT. Atomic resolution crystal structures of HIV-1 protease and mutants V82A and I84V with saquinavir. Proteins. 2007 Apr 1;67(1):232-42. PMID:17243183 doi:10.1002/prot.21304