Classification, mechanism of action for Ant retroviral drugs?

Antiretroviral drugs are classified into several categories based on their mechanism of action. These categories include:

1. Nucleoside reverse transcriptase inhibitors (NRTIs): These drugs work by inhibiting the enzyme reverse transcriptase, which is essential for the replication of the HIV virus. Examples of NRTIs include zidovudine (AZT), lamivudine (3TC), and tenofovir.

2. Non-nucleoside reverse transcriptase inhibitors (NNRTIs): These drugs also target the reverse transcriptase enzyme but do so by binding to a different site on the enzyme than NRTIs. Examples of NNRTIs include efavirenz and nevirapine.

3. Protease inhibitors (PIs): Protease is another enzyme essential for the replication of HIV. PIs work by inhibiting this enzyme, preventing the virus from maturing and infecting new cells. Examples of PIs include ritonavir, atazanavir, and darunavir.

4. Integrase inhibitors: These drugs target the enzyme integrase, which is responsible for integrating the viral DNA into the host cell's DNA. By inhibiting this enzyme, integrase inhibitors prevent the virus from replicating. Examples of integrase inhibitors include raltegravir and dolutegravir.

5. Entry inhibitors: These drugs work by blocking the entry of the virus into the host cell. There are two types of entry inhibitors: fusion inhibitors, which prevent the virus from fusing with the host cell membrane, and CCR5 antagonists, which block the CCR5 co-receptor on the host cell. Examples of entry inhibitors include enfuvirtide (fusion inhibitor) and maraviroc (CCR5 antagonist).

6. Pharmacokinetic enhancers: These drugs are used in combination with other antiretroviral drugs to boost their effectiveness by inhibiting enzymes that metabolize the drugs, increasing their concentration in the body. Examples of pharmacokinetic enhancers include ritonavir and cobicistat.

Overall, antiretroviral drugs work by targeting different stages of the HIV life cycle, ultimately preventing the virus from replicating and spreading in the body. Combination therapy with multiple antiretroviral drugs is typically used to effectively suppress the virus and prevent the development of drug resistance.

Classification of Antiretroviral Drugs

Antiretroviral drugs are classified based on their target in the HIV-1 replication cycle. There are six major classes:

I. Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
- Target: HIV-1 reverse transcriptase
- Mechanism: Terminate viral DNA synthesis by prematurely ending the growing chain

II. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
- Target: HIV-1 reverse transcriptase
- Mechanism: Bind to a different site on reverse transcriptase, blocking the binding of dNTPs

III. Protease Inhibitors (PIs)
- Target: HIV-1 protease
- Mechanism: Inhibit the cleavage of viral polyproteins into mature proteins, rendering the virus noninfectious

IV. Integrase Strand Transfer Inhibitors (INSTIs)
- Target: HIV-1 integrase
- Mechanism: Prevent the integration of viral DNA into the host genome

V. Entry Inhibitors
- Subclasses:
- CCR5 Antagonists (e.g., maraviroc)
- Fusion Inhibitors (e.g., enfuvirtide)
- Target: Viral entry into host cells
- Mechanism: Block the interaction between the virus and the host cell receptor (CCR5) or prevent the fusion of viral and host cell membranes

VI. Post-Attachment Inhibitors
- Target: Host cellular factors required for viral infection
- Mechanism: Inhibit viral uncoating, reverse transcription, or viral replication

Mechanism of Action for Selected Antiretroviral Drugs

NRTIs (e.g., tenofovir, emtricitabine)
- Phosphorylated to active triphosphate form within host cells
- Compete with natural dNTPs and incorporate into the growing viral DNA chain
- Terminate DNA synthesis prematurely due to their lack of 3'-OH group

NNRTIs (e.g., nevirapine, efavirenz)
- Bind to a hydrophobic pocket in HIV-1 reverse transcriptase
- Induce conformational changes that prevent dNTP binding and DNA synthesis

PIs (e.g., lopinavir, darunavir)
- Mimic the natural substrate of HIV-1 protease and form stable complexes with the enzyme
- Inhibit the proteolytic cleavage of viral polyproteins, leading to the formation of immature, noninfectious virus

INSTIs (e.g., raltegravir, dolutegravir)
- Bind to the active site of HIV-1 integrase
- Block the removal of the terminal nucleotides from the viral DNA and prevent its integration into the host genome