Structure and Physics of Viruses pp 599-630

Part of the Subcellular Biochemistry book series (SCBI, volume 68)

Antiviral Agents: Structural Basis of Action and Rational Design



During 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.


Antiretroviral drugs Capsid proteins DNA polymerases Drug development Fusion inhibitors Hepatitis virus Herpesviruses Human immunodeficiency virus Influenza virus Ligand docking Neuraminidase Nucleoside analogues Proteases Viral assembly Viral entry Viral replication Virtual screening 



Acquired immune deficiency syndrome


Comparative molecular field analysis


C-terminal domain


Hepatitis B virus


Human cytomegalovirus


Hepatitis C virus


Human immunodeficiency virus


Heptad repeat


Herpes simplex virus


High-throughput screening


Ligand-based virtual screening


Messenger RNA


N-acetylneuraminic acid


Nuclear magnetic resonance


Nonnucleoside RT inhibitors


N-terminal domain


Protein Data Bank


Respiratory syncytial virus


Reverse transcriptase


Structure-based virtual screening




Varicella-zoster virus


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Further Reading2

  1. Kazmierski WM (ed) (2011) Antiviral drugs: from basic discovery through clinical trials. Wiley, HobokenGoogle Scholar
  2. LaFemina RL (ed) (2009) Antiviral research: strategies in antiviral drug discovery. ASM Press, WashingtonGoogle Scholar
  3. Young DC (2009) Computational drug design: a guide for computational and medicinal chemists. Wiley, HobokenCrossRefGoogle Scholar
  4. A collection of reviews written by Dr. Eric De Clercq and published in Medicinal Research Reviews between 2008 and 2011 provide a nice summary on the design and development of many antiviral drugs, from a historical perspective and providing relevant chemical structures. References for these articles areGoogle Scholar
  5. De Clercq E (2008) The discovery of antiviral agents: ten different compounds, ten different stories. Med Res Rev 28:929–953PubMedCrossRefGoogle Scholar
  6. De Clercq E (2009) Antiviral drug discovery: ten more compounds, and ten more stories (part B). Med Res Rev 29:571–610PubMedCrossRefGoogle Scholar
  7. De Clercq E (2009) Another ten stories in antiviral drug discovery (part C): “old” and “new” antivirals, strategies, and perspectives. Med Res Rev 29:611–645PubMedCrossRefGoogle Scholar
  8. De Clercq E (2010) Yet another ten stories on antiviral drug discovery (part D): paradigms, paradoxes, and paraductions. Med Res Rev 30:667–707PubMedGoogle Scholar
  9. De Clercq E (2011) The next ten stories on antiviral drug discovery (part E): advents, advances, and adventures. Med Res Rev 31:118–160PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Centro de Biología Molecular “Severo Ochoa” (Consejo Superior de Investigaciones Científicas & Universidad Autónoma de Madrid)MadridSpain
  2. 2.Department of PharmacologyUniversidad de AlcaláMadridSpain

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