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

• Main Authors: Zuyuan Shen, Kaiyan Lou, Wei Wang
• Format: Article
• Language: English
• Published: Elsevier 2015-09-01
• Series: Acta Pharmaceutica Sinica B
• Subjects: Influenza A virus; Drug discovery; Resistance; M2 ion channel; Neuraminidase
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211383515001148

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.