Antivirals

1 Key excerpts on "Antivirals"

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  eBook - ePub

  Principles of Virology, Volume 2

  Pathogenesis and Control

  • S. Jane Flint, Vincent R. Racaniello, Glenn F. Rall, Theodora Hatziioannou, Anna Marie Skalka(Authors)
  • 2020(Publication Date)
  • ASM Press

    (Publisher)

  Fig. 8.1 ): it consists of approximately 90 antiviral drugs that have been approved to treat nine different human viral infectious diseases. This paucity reflects the many challenges that must be met in drug development. However, when available, Antivirals can have a major impact on human health. Because of their medical importance, most of our antiviral drugs are directed against infections with human immunodeficiency virus type 1, herpesviruses, and hepatitis viruses. In these cases, literally millions of lives have been saved by use of antiviral drugs.

  One major limitation in antiviral drug development is the requirement for a high degree of safety. This restriction can be difficult to surmount because virus reproduction depends on cellular functions: a compound that blocks a pathway that is critical for the virus can also have deleterious effects on the host cell. Another requirement is that antiviral compounds must be extremely potent at the site of infection: even modest reproduction in the presence of an inhibitor provides the opportunity for selection of resistant mutants. Achieving sufficient potency to block viral reproduction completely is remarkably challenging. Other limitations can be imposed by the difficulty in propagating some medically important viruses in the laboratory (e.g., hepatitis B virus and papillomaviruses) and the lack of small-animal models that faithfully reproduce infection in humans (such as measles and hepatitis C viruses). Lack of rapid diagnostic reagents has also hampered the development and marketing of antiviral drugs to treat many acute viral diseases, even when effective therapies are available. Many acute virus infections are of short duration, and by the time the patient feels ill, it is too late to impact clinical disease. Economic considerations also play a role: pharmaceutical companies mainly focus on viral diseases that can provide substantial profits.

  A Brief History of Antiviral Drug Discovery

  The first large-scale effort to find antiviral compounds began in the early 1950s with a search for inhibitors of smallpox virus reproduction. At that time, virology was in its infancy and smallpox was a worldwide scourge. Drug companies expanded efforts in the 1960s and 1970s, spurred on by increased knowledge and understanding of the viral etiology of common diseases, as well as by remarkable progress in the discovery of antibiotics to treat bacterial infections. Companies launched massive screening programs to find chemicals with antiviral activities. These antiviral discovery programs comprised

  blind screening

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