The potential of devasting pandemic influenza outbreaks has
attracted a great amount of resources and efforts in the search for
possible prevention and effective treatment methods of influenza A
infections. Currently, two main strategies against the virus are
available, which are vaccination and small molecule anti-influenza
drugs. Anti-influenza small molecule drugs present the first line of
protection against the virus during an epidemic outbreak, especially
in the early stages, as an effective vaccine usually takes at least 6
months to develop for the circulating strains. Furthermore, vaccina-
tion has limited effectiveness in treatment of immunocompromised
patients. Moreover, anti-influenza drugs have demonstrated benefit
in clinical practices in terms of shortening the disease duration and
reducing the risk of influenza-caused serious complications and
death if patients are treated in a timely fashion. For all of these
reasons, anti-influenza drugs are necessary for the control of
influenza A virus pandemics. Currently, two major classes of drugs
are approved by FDA for anti-influenza A virus treatment:
admantane-based M2 ion channel protein blockers (amantadine
and rimantadine) and neuraminidase inhibitors (oseltamivir, zana-
mivir, and peramivir). However, the continuous evolvement of
influenza A virus and the rapid emergence of resistance to current
drugs, particularly to admantanes2 and oseltamivir3,4
, has raised
great concern for a possible pandemic flu, highlighting an urgent
need for developing new anti-influenza drugs against resistant
influenza A virus. In this review, we discuss recent progress made
in small-molecule drug development to overcome influenza A virus
resistance with a focus on novel drug design strategies targeting the
mutant M2 ion channel proteins and neuraminidases, as well as
other viral proteins not associated with current drugs.
The potential of devasting pandemic influenza outbreaks hasattracted a great amount of resources and efforts in the search forpossible prevention and effective treatment methods of influenza Ainfections. Currently, two main strategies against the virus areavailable, which are vaccination and small molecule anti-influenzadrugs. Anti-influenza small molecule drugs present the first line ofprotection against the virus during an epidemic outbreak, especiallyin the early stages, as an effective vaccine usually takes at least 6months to develop for the circulating strains. Furthermore, vaccina-tion has limited effectiveness in treatment of immunocompromisedpatients. Moreover, anti-influenza drugs have demonstrated benefitin clinical practices in terms of shortening the disease duration andreducing the risk of influenza-caused serious complications anddeath if patients are treated in a timely fashion. For all of thesereasons, anti-influenza drugs are necessary for the control ofinfluenza A virus pandemics. Currently, two major classes of drugsare approved by FDA for anti-influenza A virus treatment:admantane-based M2 ion channel protein blockers (amantadineand rimantadine) and neuraminidase inhibitors (oseltamivir, zana-mivir, and peramivir). However, the continuous evolvement ofinfluenza A virus and the rapid emergence of resistance to currentdrugs, particularly to admantanes2 and oseltamivir3,4, has raisedgreat concern for a possible pandemic flu, highlighting an urgentneed for developing new anti-influenza drugs against resistantinfluenza A virus. In this review, we discuss recent progress madein small-molecule drug development to overcome influenza A virusresistance with a focus on novel drug design strategies targeting themutant M2 ion channel proteins and neuraminidases, as well asother viral proteins not associated with current drugs.
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