What is the mechanism of action of NRTI?
Nucleoside Reverse Transcriptase Inhibitors (NRTIs) inhibit reverse transcription by causing chain termination after they have been incorporated into viral DNA. For these drugs to be active they need to be phosphorylated intracellularly. This was the first group of antiretroviral agents to be used against HIV.
How do NRTIs and NNRTIs work?
NNRTIs work by binding to the HIV enzyme called reverse transcriptase, which is essential to the viral replication process, and therefore blocking HIV from making copies of itself. Dapivirine is an example of an NNRTI. NRTIs work by mimicking nucleotides that are the building blocks of viral DNA.
Why do NRTIs cause mitochondrial toxicity?
The mechanism by which NRTIs cause mitochondrial toxicity appears to be the relatively selective inhibition of human DNA polymerase-gamma: an enzyme almost exclusively relegated to the task of replicating mitochondrial DNA.
What do integrase inhibitors do?
Integrase inhibitors rely on the fact that HIV needs integrase to replicate. These drugs stop HIV from being able to make integrase. Without the help of this enzyme, HIV can’t take over the T cells to copy itself. With a combination of other HIV medications, integrase inhibitors can help keep HIV under control.
What is the mechanism of action of nevirapine?
MICROBIOLOGY Mechanism of Action: Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1. Nevirapine binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme’s catalytic site.
Is mitochondrial toxicity reversible?
Depletion of mitochondrial DNA has been reported in patients with zidovudine related myopathy, and this has been shown to be reversible on drug withdrawal.
What drugs affect the mitochondria?
Drug classes identified to cause mitochondrial toxicity are anti-diabetic drugs (thiazolidinediones, fibrates, biguanides), cholesterol lowering drugs (statins), anti-depressants (SARIs), pain medications (NSAIDs), certain antibiotics (fluroquinolones, macrolide), and anti-cancer drugs (kinase inhibitors and …
What can cause mitochondrial damage?
On a physiological level, mitochondrial dysfunction is caused by exposure to certain environmental factors (such as certain pharmaceutical drugs, occupational chemicals and cigarette smoke) or genetic abnormalities (of both mitochondrial and nuclear DNA).
How does integrase work?
Integrase catalyzes nucleophilic attack of the 3′ hydroxyl group at the ends of the processed DNA on a pair of phosphodiester bonds in the target DNA (DNA strand transfer). Cellular enzymes complete integration by repairing the resulting integration intermediate.