The first two inhibitors act on the same principle. The major difference between them is that the nucleosides need to be phosphorylated by cellular kinases. The enzyme reverse transcriptase recognizes them as regular nucleotides and inserts them into the newly synthesized DNA chain.
This process is called chain termination. Nucleoside and nucleotide inhibitors are also called competitive substrate inhibitors. Lamivudine is used for the treatment of both HIV and hepatitis B.
If there are any further questions then please do e-mail back or ask for clarifications. To be able to answer your questions about NNRTIs non-nucleoside reverse transcriptase inhibitors and NRTIs nucleoside reverse transcriptase inhibitors let me first start by explaining what a nucleoside is and how reverse transcriptase works.
DNA is the genetic code which makes us what we are. It is what determines if we have blue eyes or a wonky nose, what we look like and to some people, if we are susceptible to any genetic medical conditions. Our body is constantly renewing itself and making new cells.
It is a bit like a zip opening. The single-stranded RNA then goes on to become the proteins that make up our skin, organs, hair, nails etc. HIV alone is not able to replicate. It has to put its own genetic material into our genetic material so that we can replicate the parts of the virus ourselves.
Mitochondrial toxicity, due in large part to the high affinity of several NRTI agents for uptake by mitochondrial DNA polymerase gamma, has been demonstrated both in vitro and in vivo. New chain-terminating agents are urgently needed that address issues of improved virological potency, greater efficacy in NRTI-experienced individuals, and greater long-term safety.
The nucleotide class of reverse transcriptase inhibitor NtRTI , currently under clinical development, addresses improved potency by abbreviating the intracellular activation pathway to allow a more rapid and complete conversion to the active agent. These nucleoside monophosphate analogues are taken as masked prodrugs bearing labile lipophilic groups to facilitate penetration of target cell membranes.
Nucleoside reverse transcriptase inhibitors are analogues of natural nucleosides. Therefore, once they get attached to synthesizing viral DNA chain, the synthesis is terminated and the extending of the new strand is ceased. Thus, the synthesis of viral DNA is interrupted, halting the viral replication and multiplication processes. Ultimately, the viral infection does not spread within the host.
Once activated, they complete with natural viral nucleotides and bind to the growing strand and terminate the extension of the viral DNA. In fact, nucleoside reverse transcriptase inhibitors are analogues of natural purines and pyrimidines. Zidovudine, didanosine, stavudine, zalcitabine, lamivudine and abacavir are several drugs which are nucleoside reverse transcriptase inhibitors.
Nucleotide reverse transcriptase inhibitors are the second type of antiretroviral drugs used in the treatments of HIV and other retroviral infections. They work as competitive substrate inhibitors similar to nucleoside reverse transcriptase inhibitors.
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