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14.4 Mechanisms of other antimicrobial drugs  (Page 9/15)

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Acyclovir looks similar to guanosine except that the sugar is replaced with a short carbon chain. Step 1: Viral enzyme adds a phosphate group to acyclovir. Step 2: Human enzymes add two more phosphate groups, producing acyclovir triphosphate. Step 3: During viral DNA replication, acyclovir is added to the growing strand rather than GTP. This halts further elongation of the DNA molecule and stops viral replication.
Acyclovir is a structural analog of guanosine. It is specifically activated by the viral enzyme thymidine kinase and then preferentially binds to viral DNA polymerase, leading to chain termination during DNA replication.
Diagram showing HIV infection and locations where drugs can stop the infection. GP120 and G(42 are proteins that are on the surface of the virus and bind to CD4 receptor and CCR5. Enfuvirtide is a fusion inhibitor that blocks this process. When the virus enters, it produces DNA from RNA, this can be blocked by AZT and etravirine which are reverse-transcriptase inhibitors. Next, the viral DNA integrates into the host DNA. Raltegravir is an integrase inhibitor and blocks this step. Finally the virus is rebuild. Ritonavir is a protease inhibitor and blocks this step.
Antiretroviral therapy (ART) is typically used for the treatment of HIV. The targets of drug classes currently in use are shown here. (credit: modification of work by Thomas Splettstoesser)
Common Antiviral Drugs
Mechanism of Action Drug Clinical Uses
Nucleoside analog inhibition of nucleic acid synthesis Acyclovir Herpes virus infections
Azidothymidine/zidovudine (AZT) HIV infections
Ribavirin Hepatitis C virus and respiratory syncytial virus infections
Vidarabine Herpes virus infections
Sofosbuvir Hepatitis C virus infections
Non-nucleoside noncompetitive inhibition Etravirine HIV infections
Inhibit escape of virus from endosomes Amantadine, rimantadine Infections with influenza virus
Inhibit neuraminadase Olsetamivir, zanamivir, peramivir Infections with influenza virus
Inhibit viral uncoating Pleconaril Serious enterovirus infections
Inhibition of protease Ritonavir HIV infections
Simeprevir Hepatitis C virus infections
Inhibition of integrase Raltegravir HIV infections
Inhibition of membrane fusion Enfuviritide HIV infections
  • Why is HIV difficult to treat with antivirals?
Link to learning graphic

To learn more about the various classes of antiretroviral drugs used in the ART of HIV infection, explore each of the drugs in the HIV drug classes provided by US Department of Health and Human Services at this website.

Key concepts and summary

  • Because fungi, protozoans, and helminths are eukaryotic organisms like human cells, it is more challenging to develop antimicrobial drugs that specifically target them. Similarly, it is hard to target viruses because human viruses replicate inside of human cells.
  • Antifungal drugs interfere with ergosterol synthesis, bind to ergosterol to disrupt fungal cell membrane integrity, or target cell wall-specific components or other cellular proteins.
  • Antiprotozoan drugs increase cellular levels of reactive oxygen species, interfere with protozoal DNA replication (nuclear versus kDNA, respectively), and disrupt heme detoxification.
  • Antihelminthic drugs disrupt helminthic and protozoan microtubule formation; block neuronal transmissions; inhibit anaerobic ATP formation and/or oxidative phosphorylation; induce a calcium influx in tapeworms, leading to spasms and paralysis; and interfere with RNA synthesis in schistosomes.
  • Antiviral drugs inhibit viral entry, inhibit viral uncoating, inhibit nucleic acid biosynthesis, prevent viral escape from endosomes in host cells, and prevent viral release from infected cells.
  • Because it can easily mutate to become drug resistant, HIV is typically treated with a combination of several antiretroviral drugs , which may include reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors , and drugs that interfere with viral binding and fusion to initiate infection.

Fill in the blank

Antiviral drugs, like Tamiflu and Relenza, that are effective against the influenza virus by preventing viral escape from host cells are called ________.

neuraminidase inhibitors

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True/false

Echinocandins, known as “penicillin for fungi,” target β(1→3) glucan in fungal cell walls.

true

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Short answer

How does the biology of HIV necessitate the need to treat HIV infections with multiple drugs?

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Niclosamide is insoluble and thus is not readily absorbed from the stomach into the bloodstream. How does the insolubility of niclosamide aid its effectiveness as a treatment for tapeworm infection?

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Source:  OpenStax, Microbiology. OpenStax CNX. Nov 01, 2016 Download for free at http://cnx.org/content/col12087/1.4
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