Antiviral Drugs

Antiviral Drugs

Table of contents

  • Introduction of antiviral drugs
  • Tamiflu an antiviral drugs
  • Different drugs to treat viral illness
  • Development of anti-DNA virus drugs
  • Common Antiviral drugs use to manage HIV infection
  • Successful treatment approch for HIV/AIDS

Introduction

Viruses enter host cells and make use of host cell enzymes and constituents, it was long thought that a drug that
blocked virus multiplication would be toxic for the host. However, the discovery of inhibitors of virus-specific enzymes and replication cycle processes has led to the development of antiviral drugs.

Some important examples are:

  1. Nucleoside reverse transcriptase inhibitor.
  2. Viral protease Inhibitor.
  3. Viral fusion Inhibitor.
  4. Inhibitors of viral DNA polymerase.
  5. Blocks viral penetration and uncoating.
  6. Inhibits neuraminidase.

Tamiflu an antiviral drugs

Most antiviral drugs disrupt critical stages in a virus’s multiplication cycle. Probably the most publicized antiviral agent is Tamiflu (generically, oseltamivir phosphate) . Tamiflu inhibits the viral molecule neuraminidase, which is essential for release of newly synthesized influenza A virus particles from host cells.

Tamiflu received much attention during the 2009-2010 H1N1 influenza pandemic. While Tamiflu is not a cure for neuraminidase expressing viruses, clinical trials show that patients who take Tamiflu within 48 hours of influenza infection are relieved of flu symptoms 1.3 days faster than patients who do not take Tamiflu.

Unfortunately, prophylactic use has resulted in viral resistance to Tamiflu. It is important to recognize that Tamiflu is not a substitute for yearly flu vaccination and frequent hand washing. Amantadine and rimantadine can also be used to prevent influenza A illness. When given within the first 48 hours of infection, these drugs reduce the incidence of influenza by 50% to 70% in an exposed population. Amantadine blocks the penetration and uncoating of influenza virus particles.

Different drugs to treat viral illness

Several different drugs are commonly used to treat illnesses caused by viruses with DNA genomes. Adenine arabinoside (vidarabine) disrupts the activity of viral DNA polymerase and several other enzymes involved in DNA and RNA synthesis and function. It is given intravenously or applied as an ointment to treat herpes infections (e.g., cold sores and genital herpes).

A third drug, acyclovir, is also used in the treatment of herpes infections. Upon phosphorylation, acyclovir also inhibits viral DNA polymerase. Unfortunately, acyclovir-resistant strains of herpes have developed. Effective acyclovir derivatives are now available. Valacyclovir is an orally administered prodrug form of acyclovir. Pro drugs are inactive until metabolized. Another kind of drug, foscarnet, also inhibits the virus’s DNA polymerase, and is very effective at treating illnesses caused by herpes simplex viruses and cytomegalovirus.

Development of anti-DNA virus drugs

Several broad-spectrum anti-DNA virus drugs have been developed. A good example is the drug HPMPC, also known as cidofovir. It is effective against papovaviruses (warts), adenoviruses (respiratory diseases), herpesviruses (oral and genital sores), and poxviruses (chickenpox).

The drug acts on the viral DNA polymerase as a competitive inhibitor. It is structurally similar to deoxycytosine triphosphate (dCTP), a substrate of DNA polymerase. Thus it blocks viral DNA synthesis. HPMPC has been used primarily against cytomegalovirus but also against herpes simplex and human papillomavirus infections.

Common Antiviral drugs use to manage HIV infection

Since the early days of human immunodeficiency virus (HIV) treatment, much effort has been focused on developing new drugs. These drugs target and interfere with critical steps in the viral replicative processes.

There are now four categories of drugs used in combination to manage HIV infection:

  1. Nucleoside reverse transcriptase inhibitors (NRT is), which are nucleoside analogues that produce faulty viral DNA (e.g., azidothymidine or AZT).
  2. Nonnucleoside reverse transcriptase inhibitors (NNRT is), which prevent HIV DNA synthesis by selectively binding to and inhibiting the reverse transcriptase enzyme.
  3. Protease inhibitors (Pis), which block the activity of the HIV protease that is needed for the production of all viral protein.
  4. Fusion inhibitors (Fis), a relatively new category of drugs that prevent HIV entry into cells.
Viral infection can be interrupted by correct use of drugs that target specific components of the HIV replicative process.

Inhibition of reverse transcription, which catalyzes an early step in the multiplication cycle of the virus-the conversion of the virus’s RNA genome into double-stranded DNA, blocks viral DNA synthesis and halts HIV replication. Protease inhibitors are effective because HIV, like many RNA viruses, synthesizes polyproteins that must be cleaved into the individual proteins required for virus replication.

Protease inhibitors mimic the peptide bond that is normally attacked by the protease. Three of the most used Pis are saquinavir, indinavir, and ritonavir. Fusion inhibitors are particularly interesting as an effective blockade to viral entry into host cells, essentially preventing disease.

Successful treatment approch for HIV/AIDS

The most successful treatment approach to date in combating HIV/AIDS is to use drug combinations. Most effective is a cocktail of agents given at high dosages to prevent the development of drug resistance. For example, the combination of the two reverse transcriptase inhibitors AZT and 3TC, and the protease inhibitor ritonavir reduces HIV concentrations in plasma almost to zero.

However, the treatment does not eliminate proviral HIV DNA that still resides in certain cells of the immune system (e.g., memory T cells) and possibly other cells. Thus with proper treatment, the virus often disappears from a patient’s blood and drug-resistant strains do not seem to arise. But because HIV can remain dormant in memory T cells, it can survive drug cocktails and reactivate. Thus patients are not completely cured with drug treatment, requiring drug therapy for life.

Unfortunately, side effects can be very severe, and treatment is prohibitively expensive for those without medical insurance. Globally, the vast majority of HIV-positive individuals do not have access to effective combination therapy.

Recent studies have led the CDC to recommend a pre-HIV exposure prophylaxis (prevention) strategy to men and women who have sex with HIV-infected partners. The daily oral dose of two NRTIs was strongly correlated with reduced HIV transmission among uninfected individuals exposed to the virus through sexual contact.

Reference and sources

  • https://www.researchgate.net/publication/7977798_Agents_and_strategies_in_development_for_improved_management_of_herpes_simplex_virus_infection_and_disease
  • https://textarchive.ru/c-1513693-p3.html
  • https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5103a1.htm
  • https://quizlet.com/314905522/microbiology-5414-final-exam-study-guide-flash-cards/
  • https://www.accessscience.com/content/virus/733500
  • https://en.wikipedia.org/wiki/Antiviral_drug
  • https://quizlet.com/207086621/micro-chapter-9-flash-cards/
  • https://apps.who.int/iris/bitstream/handle/10665/206000/B0184.pdf?sequence=1&isAllowed=y
  • https://web.wpi.edu/Pubs/E-project/Available/Eproject-042911-162135/unrestricted/Reinhold_Gildemeister_MQP_Final.pdf

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