Authors: Uchide, Noboru; Toyoda, Hiroo

Source: Anti-Infective Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Infective Agents), Volume 7, Number 2, April 2008 , pp. 73-83(11)

Publisher: Bentham Science Publishers

Abstract:

The human beings face the threat of a highly pathogenic avian influenza virus. The use of anti-influenza drugs is receiving much greater attention to playing an important role as a first-line defense against a new pandemic of influenza virus infection. However, influenza viruses resistant to currently available anti-influenza drugs, such as the M2 proton channel inhibitors and the neuraminidase inhibitors, are emerged frequently during the treatment with drugs. This suggests the need for development of new anti-influenza drugs utilizing alternative antiviral mechanisms and consideration of using anti-influenza drug combinations. Recent studies have clarified that the pathogenesis of influenza virus infection involves not only the virus replication-associated apoptotic cell death in the infected cells, but also the injury of noninfected cells by reactive oxygen species derived from macrophages and neutrophils infiltrated into the virus-infected organs. These findings provide a possibility that an agent with all of the following antiviral, anti-apoptosis and antioxidant activities can be a drug of choice for the treatment of patients with influenza virus infection. Selected antioxidants, such as pyrrolidine dithiocarbamate, N-acetyl-L-cysteine, glutathione, nordihydroguaiaretic acid and thujaplicin, possessed all of these activities. The combination of antioxidants, such as superoxide dismutase and N-acetyl-L-cysteine, with antiviral drug ribavirin synergistically reduced the lethal effect of influenza virus infection. Accumulating number of evidence highlights a potential of selected antioxidants for influenza chemotherapy and a possibility that combination of antioxidants with current anti-influenza drugs can improve usual influenza chemotherapy.

Keywords: Influenza virus; antioxidants; apoptosis; macrophage; monocyte differentiation-inducing (MDI) factors; phagocytosis; reduced nicotinamide adenine dinucleotide phosphat; reactive oxygen species

Document Type: Research article

DOI: http://dx.doi.org/10.2174/187152108783954605

Publication date: 2008-04-01

More about this publication?

• Anti-Infective Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new anti-infective agents.
  Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in anti-infective medicinal chemistry.
  
  Anti-Infective Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in anti-infective drug discovery.

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