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Differences Between Nucleoside and Nucleotide Reverse Transcriptase Inhibitors

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Reverse Transcriptase: An Introduction

MVSAT 2024

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.

  1. Nucleoside reverse transcriptase inhibitors

  2. Nucleotide reverse transcriptase inhibitors

  3. Non-nucleoside reverse transcriptase inhibitors

  4. 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

Nucleoside Reverse Transcriptase Inhibitors

Nucleotide Reverse Transcriptase Inhibitors

These drugs undergo three steps of phosphorylation inside the cell or intracellularly.

These cells do not experience the process of phosphorylation to get activated.

Phosphorylation is a must to activate.

No need to phosphorylate initially to get active.

Examples are zidovudine and stavudine.

Examples are tenofovir.


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?

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FAQs on Differences Between Nucleoside and Nucleotide Reverse Transcriptase Inhibitors

1. Write the steps of the reverse transcription process.

Reverse transcription is the process used by RNA of viruses to make DNA. This process starts when the virus enters the cytoplasm of the host cell. 

The main steps of this process are:

  1. Lysyl tRNA acts as a primer and is hybridised into the complementary part of a virus

  2. Then reverse transcriptase add nucleotides on 3' end 

  3. The tRNA jumps 3'end of the virus

  4. The complementary DNA is further extended

  5. The tRNA primer leaves and jumps happen 

  6. At last, both strands are extended to form a complete double strand copy of the original virus genetic material

2. What is Islatravir?

Islatravir is the investigational drug for HIV. It is a type of nucleoside reverse transcriptase translocation inhibitor. It is used for the treatment of HIV aids and prophylaxis. It inhibits the function of certain strains of HIV. This drug prevents multiplying HIV and thus reduces the number of virus particles through various mechanisms.  It provides rapid suppression of the virus. 


There are various side effects of this drug-  the majority of side effects are of mild intensity such as diarrhoea, nausea, and vomiting.

3. What are two different mechanisms of action for antiretroviral therapy?

The two other mechanisms for antiretroviral treatment are as follows:

  1. Block reverse transcriptase to damage copying of HIV genetic code. By blocking the reverse transcriptase enzyme, we can prevent the process of the reverse transcription and hence reduce the number of virus particles.

  2. Block protease enzyme and hence prevent maturation of the new virions. Protease is a proteolytic enzyme that breaks down the protein and hence helps in the maturation of virus particles. By inhibiting  this enzyme we can inhibit the virus formation 


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