Pharmacology
Summary
Entry inhibitors, fusion inhibitors, and integrase inhibitors each play a role in hindering the HIV viral life cycle. The viral structural genes, gag, pol, and env, code for protein precursors that form the new virion. The gag structural gene codes for virion core proteins which include P7 and P24. The env structural gene produces the 'envelope' proteins essential for invading the next host cell. These envelope proteins, gp41 and gp120, are crucial for infiltration of the membrane of the next host cell, where entry inhibitors and fusion inhibitors play a role. Maraviroc, an entry inhibitor, binds to the CCR5 receptor on the host cell to block virus entry, while enfuvirtide, a fusion inhibitor, binds to the gp41 viral surface proteins to hinder fusion.
If HIV successfully enters a host cell, viral RNA is converted into double-stranded DNA by an enzyme called reverse transcriptase. This is where specific antiretroviral drugs inhibit the action of reverse transcriptase. Integrase, another viral enzyme which is encoded by the pol structural gene, helps integrate the viral DNA into the host DNA, a step inhibited by integrase inhibitors like raltegravir. This inhibitor disrupts the ability of HIV DNA to integrate into host chromosomes. Resistance to these antiretroviral drugs can arise from mutations in HIV’s env and pol genes.
Lesson Outline
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FAQs
Maraviroc is an entry inhibitor that plays a critical role in the treatment of HIV infection. It works by binding to the chemokine receptor CCR5 on the surface of the host cell, preventing the surface glycoprotein gp120 of HIV from attaching to it. This effectively blocks the virus from gaining entry into the host cell and subsequently infecting it.
Fusion inhibitors, such as enfuvirtide, play a crucial role in the HIV treatment regimen. They work by binding to the surface glycoprotein gp41 of the HIV virus. This prevents gp41 from facilitating fusion of the virus with the host cell, thereby effectively stopping the virus from entering and infecting the host cells.
Integrase inhibitors like raltegravir are key medications in the treatment of HIV. They work by binding to the viral enzyme integrase, which is responsible for integrating the viral DNA with the host cell DNA. Inhibition of integrase hinders this integration process, thus preventing the virus from replicating inside the host cell.
While integrase inhibitors are effective in the treatment of HIV, they may have some side effects. One notable adverse reaction is rhabdomyolysis, a serious syndrome due to a direct or indirect muscle injury. Other side effects can include weight gain, insomnia, dizziness, and psychiatric symptoms.
The entry inhibitor maraviroc specifically binds to CCR5, preventing HIV from entering the host cell. However, not all HIV strains use CCR5 to enter host cells. Some strains of HIV use the CXCR4 receptor. In cases where the virus is identified to use CXCR4, other treatment methods, including different entry inhibitors, fusion inhibitors, and antiretroviral therapy, may be employed to effectively manage the disease.
