New small-molecule drug design strategies for fighting resistant influenza A.
10.1016/j.apsb.2015.07.006
- Author:
Zuyuan SHEN
1
;
Kaiyan LOU
1
;
Wei WANG
2
;
Author Information
1. Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, and State Key Laboratory of Bioengineering Reactor, East China University of Science and Technology, Shanghai 200237, China.
2. Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, and State Key Laboratory of Bioengineering Reactor, East China University of Science and Technology, Shanghai 200237, China
- Publication Type:Journal Article
- Keywords:
Drug discovery;
Influenza A virus;
M2 ion channel;
Neuraminidase;
Resistance
- From:
Acta Pharmaceutica Sinica B
2015;5(5):419-430
- CountryChina
- Language:English
-
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.