How Do NRTIs and NtRTIs Differ in HIV Treatment Mechanisms?
As we all know most viruses have RNA as genetic material. Through the process of transcription, DNA makes RNA. Do you know how DNA is made from RNA? Or what is the function of reverse transcriptase enzymes? In this article, we are going to study reverse transcriptase enzymes and reverse transcriptase inhibitors, and the types of reverse transcriptase inhibitors. We will also learn about the differences and similarities between nucleoside and nucleotide reverse transcriptase.
Reverse Transcriptase
Reverse transcription is a process of converting RNA into complementary DNA. This process mostly occurs in viruses that have RNA as genetic material.
Reverse transcriptase is an enzyme used for this process. There are two types of reverse transcriptase- nucleoside and nucleotide reverse transcriptase.
Reverse Transcriptase Inhibitors
Reverse transcriptase inhibitors are drugs that inhibit the activity of reverse transcriptase enzymes and these are used to treat HIV infection.
There are mainly four forms of reverse transcriptase inhibitors.
Nucleoside reverse transcriptase inhibitors
Nucleotide reverse transcriptase inhibitors
Non-nucleoside reverse transcriptase inhibitors
Nucleoside reverse transcriptase translocation inhibitors
Nucleoside Reverse Transcriptase
Nucleoside reverse transcriptase inhibitor inhibits the activity of nucleoside reverse transcriptase enzymes. This inhibitor works by competitive inhibition and inhibits nucleoside reverse transcriptase's activity or functions. These drugs comprise the first class of antiretroviral drugs. A few examples of nucleoside reverse transcriptase inhibitors are zidovudine, stavudine, didanosine, etc.
Nucleotide Reverse Transcriptase Inhibitors
Nucleotide reverse transcriptase also works as a competitive inhibitor as nucleoside reverse transcriptase inhibitors. These are the second type of antiretroviral drugs. This drug also blocks the reverse transcriptase enzyme. Examples of nucleotide reverse transcriptase inhibitor tenofovir.
Difference Between Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
Similarities Between Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
Both of these drugs are used to treat antiretroviral infections.
They work by competitive inhibitions
Both these drugs work as chain terminators.
Both these types of drugs lack hydroxyl groups.
The mechanism of action of both of these drugs is the same.
These drugs may have side effects because they also act on host cells.
Side effects of these drugs are vomiting, diarrhoea, stomach problems, and headaches.
Important Questions
1. How do nucleotide and nucleoside reverse transcriptase inhibitors work?
Ans: These drugs work by blocking the reverse transcriptase inhibitors. HIV viruses use reverse transcriptase enzymes to make cDNA from RNA. Thus to treat aids disease we need to inhibit the reverse transcriptase enzyme
2. Which enzyme is used in reverse transcription?
Ans: Reverse transcriptase is the enzyme used in the process of reverse transcription.
Conclusion
Reverse transcriptase is an enzyme that converts RNA into cDNA. Reverse transcriptase inhibitors are the drugs used to inhibit the function of reverse transcriptase and hence stop the process of reverse transcription. There are four forms of reverse transcriptase inhibitors. These include nucleoside reverse transcriptase inhibitors, nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and nucleoside reverse transcriptase translocation inhibitors. We have also discussed the differences between nucleoside and nucleotide reverse transcriptase Inhibitors and the similarities between them.
Practice Questions
1. What is the mechanism of action of nucleoside reverse transcriptase inhibitors?
2. What are the examples of nucleoside reverse transcriptase inhibitors?
3. Why is cDNA used instead of DNA?
4. Who discovered the reverse transcription?
5. How do reverse transcripts work?
FAQs on Nucleoside vs Nucleotide Reverse Transcriptase Inhibitors: Key Differences
1. What is the fundamental difference between a nucleoside and a nucleotide?
The fundamental difference lies in their chemical composition. A nucleoside consists of a nitrogenous base attached to a sugar molecule (like ribose or deoxyribose). A nucleotide is a nucleoside that has one or more phosphate groups attached to the sugar. This phosphate group is the key structural addition that distinguishes a nucleotide from a nucleoside.
2. What is the primary operational difference between Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTIs)?
The primary difference is in their activation process within the host cell. Both drug types work by terminating the construction of viral DNA. However, Nucleoside RTIs are administered as inactive prodrugs and must undergo phosphorylation (the addition of phosphate groups) by host cell enzymes to become active. In contrast, Nucleotide RTIs are designed to be closer to the active form, requiring fewer phosphorylation steps to become effective. This often allows them to act more quickly.
3. How do Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) differ in their mechanism of action?
They differ completely in how they inhibit the reverse transcriptase enzyme:
- NRTIs (Nucleoside/Nucleotide Reverse Transcriptase Inhibitors) are competitive inhibitors. They act as faulty building blocks by mimicking natural nucleosides/nucleotides. The enzyme mistakenly incorporates them into the growing viral DNA chain, which then halts further elongation.
- NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors) are non-competitive inhibitors. They do not compete with natural nucleosides. Instead, they bind to a different site on the reverse transcriptase enzyme, known as an allosteric site, which changes the enzyme's shape and makes it non-functional.
4. What is the role of the reverse transcriptase enzyme in a retrovirus like HIV?
The reverse transcriptase enzyme is crucial for the replication of retroviruses. Its primary role is to perform reverse transcription, which is the process of converting the virus's single-stranded RNA genome into a double-stranded DNA copy. This newly created viral DNA can then be integrated into the host cell's chromosome, allowing the virus to take over the cell's machinery to produce new viral particles.
5. Why is it necessary for Nucleoside RTIs to be activated by host cell enzymes?
It is necessary because the viral reverse transcriptase enzyme can only recognise and use the triphosphate form of nucleosides to build the DNA chain. Nucleoside RTIs are supplied as simple nucleoside analogues. Therefore, they rely on the host cell's own enzymes (kinases) to add the required three phosphate groups. This activation process, called phosphorylation, converts the inactive drug into a molecular mimic that the viral enzyme will mistakenly use, thereby blocking viral DNA synthesis.
6. If reverse transcriptase is blocked, how does this stop the virus from replicating?
Blocking the reverse transcriptase enzyme breaks a critical step in the retroviral life cycle. Without a functional reverse transcriptase enzyme, the virus cannot convert its RNA genome into DNA. Since the integration of viral DNA into the host cell's genome is an essential prerequisite for replication, blocking this step effectively prevents the virus from hijacking the cell's machinery. Consequently, no new virus particles can be produced, and the infection cannot progress.
7. What are some common examples of Nucleoside and Nucleotide Reverse Transcriptase Inhibitors?
Several NRTIs are used in antiretroviral therapy. Common examples include:
- Nucleoside RTIs: Zidovudine (AZT), the first approved drug for HIV, as well as Lamivudine and Abacavir.
- Nucleotide RTIs: Tenofovir is the most prominent example of a nucleotide analogue inhibitor.
