New small-molecule drug design strategies for fighting resistant influenza A

Zuyuan Shen, Kaiyan Lou, Wei Wang

Research output: Contribution to journalReview articlepeer-review

51 Scopus citations

Abstract

Influenza A virus is the major cause of seasonal or pandemic flu worldwide. Two main treatment strategies-vaccination and small molecule anti-influenza drugs are currently available. As an effective vaccine usually takes at least 6 months to develop, anti-influenza small molecule drugs are more effective for the first line of protection against the virus during an epidemic outbreak, especially in the early stage. Two major classes of anti-influenza drugs currently available are admantane-based M2 protein blockers (amantadine and rimantadine) and neuraminidase (NA) inhibitors (oseltamivir, zanamivir, and peramivir). However, the continuous evolvement of influenza A virus and the rapid emergence of resistance to current drugs, particularly to amantadine, rimantadine, and oseltamivir, have raised an urgent need for developing new anti-influenza drugs against resistant forms of influenza A virus. In this review, we first give a brief introduction of the molecular mechanisms behind resistance, and then discuss new strategies in small-molecule drug development to overcome influenza A virus resistance targeting mutant M2 proteins and neuraminidases, and other viral proteins not associated with current drugs.

Original languageEnglish (US)
Pages (from-to)419-430
Number of pages12
JournalActa Pharmaceutica Sinica B
Volume5
Issue number5
DOIs
StatePublished - Sep 1 2015
Externally publishedYes

Keywords

  • Drug discovery
  • Influenza A virus
  • M2 ion channel
  • Neuraminidase
  • Resistance

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)

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