Antiviral Drugs Targeting Influenza Virus Surface Proteins: A Computational Structural Biology Approach

• Igarashi Manabu

  Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control

Bibliographic Information

Other Title

• インフルエンザウイルスタンパク質の計算科学的解析
• Symposium Review インフルエンザウイルスタンパク質の計算科学的解析
• Symposium Review インフルエンザウイルスタンパクシツ ノ ケイサン カガクテキ カイセキ

Abstract

  For the prevention and control of infectious viral diseases, vaccines and antiviral drugs targeting viral proteins are of great importance. Amino acid substitutions in viral proteins occasionally cause the emergence of antibody-escape and drug-resistant mutants. With regard to this, we have studied the proteins of several viruses, especially the influenza A virus, by using techniques of computational chemistry and biology such as molecular modeling, molecular docking, and molecular dynamics simulations. Influenza A virus is a zoonotic pathogen that is transmitted from animals to humans. This virus has two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). The HA of influenza viruses plays a key role in the initiation of viral infection. And HA is also the major target of antibodies that neutralize viral infectivity. Some amino acid substitutions in the antigenic epitope on HA could decrease the interaction between HA and antibodies, leading to the generation of antigenic variants with novel antigenic structures of HA. In addition, HA protein seems to be a favorable target for anti-influenza drugs, but effective HA inhibitors have not been developed due to the emergence of drug-resistant viruses with amino acid substitutions on the HA. To understand how amino acid substitutions affect changes in drug susceptibility, we have been computationally analyzing the three-dimensional structures of influenza virus proteins. In this paper, we review the results obtained through our current analysis.<br>

Journal

• YAKUGAKU ZASSHI

  YAKUGAKU ZASSHI 135 (9), 1015-1021, 2015-09-01

  The Pharmaceutical Society of Japan

Keywords

• influenza virus
• molecular dynamics
• docking
• homology modeling
• anti-influenza drug
• monoclonal antibody

Details

• CRID: 1390282681104136960
• NII Article ID: 130005096687
• NII Book ID: AN00284903
• DOI: 10.1248/yakushi.15-00175-3
• ISSN: 13475231
• ISSN: 00316903
• NDL BIB ID: 026711641
• PubMed: 26329546
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026711641
• Web Site: https://www.jstage.jst.go.jp/article/yakushi/135/9/135_15-00175-3/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016154399
• Text Lang: ja
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• Abstract License Flag: Disallowed