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Title

Antiviral agents: structural basis of action and rational design

AuthorsMenéndez-Arias, Luis ; Gago, Federico
KeywordsHuman
Hepatitis virus
Fusion inhibitors
Drug development
DNA polymerases
Capsid proteins
Antiretroviral drugs
Herpesviruses
Issue Date2013
PublisherPlenum Press
CitationSub-Cellular Biochemistry 68: 599- 630 (2013)
AbstractDuring the last 30 years, significant progress has been made in the development of novel antiviral drugs, mainly crystallizing in the establishment of potent antiretroviral therapies and the approval of drugs inhibiting hepatitis C virus replication. Although major targets of antiviral intervention involve intracellular processes required for the synthesis of viral proteins and nucleic acids, a number of inhibitors blocking virus assembly, budding, maturation, entry or uncoating act on virions or viral capsids. In this review, we focus on the drug discovery process while presenting the currently used methodologies to identify novel antiviral drugs by using a computer-based approach. We provide examples illustrating structure-based antiviral drug development, specifically neuraminidase inhibitors against influenza virus (e.g. oseltamivir and zanamivir) and human immunodeficiency virus type 1 protease inhibitors (i.e. the development of darunavir from early peptidomimetic compounds such as saquinavir). A number of drugs in preclinical development acting against picornaviruses, hepatitis B virus and human immunodeficiency virus and their mechanism of action are presented to show how viral capsids can be exploited as targets of antiviral therapy.
URIhttp://hdl.handle.net/10261/117073
Identifiersissn: 0306-0225
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