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In fluenza A virus is the major cause of seasonal or pandemic flu worldwide. Two main treatment strategies–vaccination and small molecule anti-in fluenza drugs are currently available. As an effective vaccine usually takes at least 6 months to develop, anti-in fluenza small molecule drugs are more effective for the fi rst line of protection against the virus during an epidemic outbreak, especially in the early stage. Two major classes of anti-in fluenza 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 in fluenza 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-in fluenza drugs against resistant forms of in fluenza A virus. In this review,we fi rst give a brief introduction of the molecular mechanisms behind resistance, and then discuss new strategies in small-molecule drug development to overcome in fluenza A virus resistance targeting mutant M2 proteins and neuraminidases, and other viral proteins not associated with current drugs.
Two major treatment strategies-vaccination and small molecule anti-in fluenza drugs are currently available. As an effective vaccine usually takes at least 6 months to develop, anti-in fluenza small molecule drugs are more effective for the fi rst line of protection against the virus during an epidemic outbreak, especially in the early stage. Two major classes of anti-in fluenza 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 in fluenza 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-in fluenza drugs against resistant forms of in fluenza A virus. In this review, we fi rst give a brief introduction of the molecular mechanisms behind r esistance, and then discuss new strategies in small-molecule drug development to overcome in fluenza A virus resistance targeting mutant M2 proteins and neuraminidases, and other viral proteins not associated with current drugs.