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Antiviral Drug – Mode of Action

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Table of Contents

Antiviral drug referred to those drugs or chemical agents that are used for the treatment of viral infection. There are present several types of antiviral drugs that are used for the treatment of viral infections such as Amantadine, Acyclovir, Azidothymidine, Ganciclovir, Abacavir. Each of these antiviral drugs follows a different mechanism. The variation in their mechanism depends on the types of virus.

1. Amantadine Antiviral Drug


Antiviral drug mode of action - Amantadine
Figure: Mode of Action of Amantadine | Image Source: Wikipedia
  • Amantadine is used for the prophylactic or symptomatic treatment of influenza A, though this drug is no longer recommended due to drug resistance.
  • This drug also used as an antiparkinsonian agent, for the treatment of extrapyramidal reactions, and for postherpetic neuralgia.

Mode of Action of Amantadine

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    • The mechanism of this drug is not well understood but is thought to, Amantadine helps in secretion of dopamine from the nerve endings of the brain cells, then it stimulates norepinephrine response.
    • Also thought to, Amantadine interferes with the release of infectious viral nucleic acid into the host cell by the interaction with the transmembrane domain of the M2 (an ion channel) protein of the virus. It also appears to prevent virus assembly during replication in some cases.
    • Amantadine also has an N-methyl-D-aspartate receptor antagonistic effect.

2. Acyclovir Antiviral Drug

  • Acyclovir also called as acyclovir.
  • Acyclovir drugs used for the treatment of herpes simplex virus infections, chickenpox, and shingles.
  • Aciclovir can be administered through oral route or can be applied as a cream, or by injected.
  • Common side effect of this drug is nausea and diarrhea, and serious side effects are kidney problems and low platelets.

Mode of Action of acyclovir

    • At first viral thymidine kinase convert Acyclovir into aciclovir monophosphate.
    • Acyclovir monophosphate is converted into a diphosphate form with the help of enzyme guanylate kinase.
    • Then this aciclovir diphosphate converted into aciclovir triphosphate (ACV-TP) with the help of nucleoside diphosphate kinase, pyruvate kinase, creatine kinase, phosphoglycerate kinase, succinyl-CoA synthetase, phosphoenolpyruvate carboxykinase and adenylosuccinate synthetase.
    • ACV-TP has a higher affinity for viral DNA polymerase than cellular DNA polymerase.
    • Which then ACV-TP competitively inhibits viral DNA polymerase then incorporates into and terminates the growing viral DNA chain, and inactivates the viral DNA polymerase.

3. Azidothymidine Antiviral Drug

  • Azidothymidine also known as Zidovudine.
  • Azidothymidine is a analog of thymidine
  • Azidothymidine used for the treatment or prevention of HIV/AIDS.
  • This drug can be used by mouth or by slow injection into a vein.
  • Azidothymidine used to prevent the spread of HIV/AIDS from mother-to-child during birth or after a needlestick injury or other potential exposure.
  • Common side effect of this drug is headaches, fever, nausea, and serious side effects include liver problems, muscle damage, and high blood lactate levels.

Mode of Action of Azidothymidine

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    • Azidothymidine or zidovudine is a prodrug which phosphorylate its active 5′-triphosphate metabolite and form a zidovudine triphosphate (ZDV-TP).
    • Zidovudine triphosphate (ZDV-TP) competes with endogenous nucleotides for incorporation into the viral DNA.
    • And, Once it incorporated it will initiate the chain termination due to the lack of a 3’ OH group.

4. Ganciclovir Antiviral Drug

  • Ganciclovir used for the treatment of cytomegalovirus (CMV) infections.
  • This drug also has activity against nearly all herpesviruses and little activity against vaccina virus, human papillomavirus, or RNA viruses such as influenza A.
  • The antiviral activity of Ganciclovir helps to inhibit virus replication.

Mode of Action of Ganciclovir

    • Thymidine kinase catalyzes the phosphorylation of ganciclovir to the monophosphate.
    • Then this monophosphate subsequently converted into the Ganciclovir diphosphate with the help of a cellular enzyme, guanylate kinase.
    • Then Ganciclovir diphosphate converted into Ganciclovir triphosphate by a number of cellular enzymes.
    • Next, this newly formed Ganciclovir triphosphate competitively inhibits the incorporation of deoxyguanosine triphosphate into elongating DNA and leading to the formation of ‘faulty’ DNA.
    • Now ganciclovir triphosphate is started to incorporate into the DNA strand by replacing many of the adenosine bases. This results in the prevention of DNA synthesis, as phosphodiester bridges can longer be built, destabilizing the strand.
    • Ganciclovir inhibits viral DNA polymerases and does cellular polymerase more effectively than it does cellular polymerase.
    • The chain elongation is continued when ganciclovir is removed.

5. Abacavir Antiviral Drug

  • Abacavir commercially known as Ziagen.
  • Abacavir used for the prevention or treatment of HIV/AIDS.
  • Common side effects of Abacavir include vomiting, trouble sleeping, fever, feeling tired, and severe side effects include hypersensitivity, liver damage, and lactic acidosis.

Mode of Action of Abacavir

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    • Abacavir is a Nucleoside Analog Reverse Transcriptase Inhibitor (NRTI), which intracellularly phosphorylated to carbovir triphosphate, and then incorporated into the HIV DNA during reverse transcription. Carbovir triphosphate lacks a 3′-OH group and which results in chain termination.

Reference

  • https://www.drugbank.ca/drugs/DB00915
  • http://www.antimicrobe.org/drugpopup/amantadine.htm
  • https://www.drugbank.ca/drugs/DB00787
  • http://www.antimicrobe.org/drugpopup/acyclovir.htm
  • https://en.wikipedia.org/wiki/Aciclovir#Mechanism_of_action
  • http://www.antimicrobe.org/drugpopup/zidovudine.htm
  • https://en.wikipedia.org/wiki/Zidovudine#Mechanism_of_action
  • http://www.antimicrobe.org/drugpopup/Ganciclovir.htm
  • https://www.nature.com/articles/s41422-020-0282-0

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