Human immunodeficiency virus (HIV) is a retrovirus that progressively destroys CD4+ lymphocytes, making the body susceptible to attack by foreign, infectious agents and numerous forms of cancer. Maturation is the last step in the HIV life cycle. It is the step in which the HIV proteins properly assemble and are released from the infected cells into the plasma, thus spreading the HIV virus, infecting and destroying CD4+ T cells and further weakening the immune system. HIV maturation inhibition drugs inhibit the assembly of complete, functional viral particles that are able to infect new CD4+ T cells.
Bevirimat Dimeglumine
PA-457, also known as bevirimat dimeglumine, is the first anti-HIV maturation drug produced in the United States. According to Ncbi.nih.gov, a U.S. government-funded national resource for biological research, bevirimat inhibits HIV replication by inhibiting the final step in the gag processing cascade, the assembly of viral particles and formation of the outer protective coat.This results in an HIV virus that has a defective outer core and noninfectious viral particles. The outer core and viral particles are essential in the entry and replication of the viral DNA in CD4+ T cells. Thus the released HIV virus is unable to infect CD4+ T cells and further destroy one's immune cells. Due to this novel mechanism of action, PA-457 has also been found effective against HIV strains that are resistant to all classes to antiretroviral drugs.
PA1050040
PA1050040 is a second generation HIV maturation inhibitor drug, chemically analogous to bevirimat dimeglumine. Similar to bevirimat dimeglumine, PA10540040 inhibits HIV replication by inhibiting the final step in the gag processing cascade thus producing a defective outer core and the release of noninfectious virus particles from infected CD4+ T cells. Additional, Panacos.com notes that PA1050040, is active against HIV isolates resistant to bevirimat dimeglumine.(reference 2)
Vivecon
Vivecon is a maturation inhibitor drugs that is under development. Similar to PA1050040 and bevirimat dimeglumine, Vivecon in inhibits the gag processing cascade. Vivecon binds to the gag proteins and prevents its cleavage into functional viral particles thus releasing noninfectious virus particles. According to Hivandhepatitis.com, Vivecon is in phase 2a of the clinical trials and has proven to be safe in both in-vitro and in-vivo models. (reference 3)
References
- Pubmed Central: Safety and Pharmacokinetics of Bevirimat (PA-457), a Novel Inhibitor of Human Immunodeficiency Virus Maturation, in Healthy Volunteers[down-pointing small open triangle]
- Panacos: Characterization of PA1050040, a second-generation HIV-1 maturation inhibitor
- HIV and AIDS articles: Phase 1 Trial of HIV Maturation Inhibitor Vivecon (MPC-9055) Completed in Healthy Volunteers
