title: New small-molecule drug design strategies for fighting resistant influenza A.
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.
authors.affiliation: 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.
authors.forename: Zuyuan
authors.initials: Z
authors.lastname: Shen
authors.affiliation: 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.
authors.forename: Kaiyan
authors.initials: K
authors.lastname: Lou
authors.affiliation: 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 ; Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, NM 87131-0001, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
keywords: Drug discovery; Influenza A virus; M2 ion channel; Neuraminidase; Resistance