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Reverse Transcriptase Inhibitors

Let me move on to reverse transcriptase inhibitors and let’s see how it works. This is the helper t-cell. When the virus or the HIV virus attack helper t-cell, the viral RNA and reverse transcriptase entered into the cell. The reverse transcriptase makes it DNA copy of the viral RNA and that’s why you know the HIV virus is a retrovirus because the genetic information is coded from the RNA onto the DNA. And the viral RNA is then incorporated in the healthy T cells DNA. And they replicate. Now the HIV virus takes over. And kill the T cells.
Now if we can block the enzyme here or block the actual incorporation of the viral DNA into the T cells DNA, and we will be able to stop the process and stop the replication of the viral DNA in the T cell. Now based on those two mechanisms, we have tow types of RTIs. Competitive RTI’s. They compete with the incorporation of viral DNA into the T cell DNA. If the competition site is at the nucleoside, then it is called a nucleoside RTI, for example, the Retrovir If the competition site is at the nucleotide and then it’s called nucleotide RTI. For example, the Viread. Non-competitive RTIs is…
They do not compete it with the incorporation of viral DNA but simple inhibit the movement of the protein domain of the enzyme. Now, for example, the Sustiva. Here are the products. Non-competitive substrate inhibitors and the Nucleotide RTIs.

When HIV infects a cell, reverse transcriptase copies the viral single-stranded RNA genome into a double-stranded viral DNA. The viral DNA is then integrated into the host chromosomal DNA, which then allows host cellular processes to reproduce the virus. RTIs block reverses transcriptase’s enzymatic function and prevent completion of synthesis of the double-stranded viral DNA, thus preventing HIV from multiplying. RTIs are not biologics by convention since they are small chemical entities.

Reverse-transcriptase inhibitors (RTIs) are a class of antiretroviral drugs used to treat HIV infection or AIDS, and in some cases, hepatitis B. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase that is required for replication of HIV and other retroviruses. The inhibitory mechanism is depicted in the sketch. There are two types of RTIs: Competitive RTIs compete with the incorporation of viral DNA into host T cell DNA, such as zidovudine (nucleoside RTI) and Tenofovir (Nucleotide RTI). Non-competitive RTIs inhibit the movement of protein domains of reverse transcriptases, such as efavirenz. Currently authorized by the FDA for passionate use in COVID19 infection, remdesivir is a transcriptase inhibitor.

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