Potential Role of Endonuclease Inhibition and Other Targets in the Treatment of Influenza.
BACKGROUND
Influenza is a single-stranded RNA virus that is highly contagious and infects millions of people in the U.S. annually. Due to complications, approximately 959,000 people were hospitalized and another 79,400 people died during the 2017-2018 flu season. While the best methods of prevention continue to be vaccination and hygiene, antiviral treatments may help reduce symptoms for those who are infected. Until recently, the only antiviral drugs in use have been the neuraminidase inhibitors: oseltamivir, zanamivir, and peramivir.


OBJECTIVE
We reviewed novel drug targets that can be used in the treatment of influenza, particularly in the case of neuraminidase inhibitor-resistant strains that may emerge.


RESULTS
More recently, a drug with a new mechanism of action has been approved. Baloxavir marboxil inhibits the influenza cap-dependent endonuclease that is needed for the virus to initiate replication within the host cell. This endonuclease target is within the polymerase acid (PA) subunit of RNA polymerase. Since the RNA-dependent RNA polymerase consists of two other subunits, polymerase basic 1 and 2, RNA polymerase has several targets that prevent viral replication. Other targets still under investigation include viral kinases, endocytosis, and viral fusion.


CONCLUSION
Due to the possibility of viral mutations and resistance, it is important to have antivirals with different mechanisms available, especially in the case of a new pandemic strain. Several novel antivirals are within various stages of development and may represent new classes of treatments that can reduce symptoms and complications in those patients who may be at higher risk.
['Szollosi|Doreen|D|', 'Bill|Ashley|A|']
D000998:Antiviral Agents D002986:Clinical Trials as Topic D003988:Dibenzothiepins D024882:Drug Resistance, Viral D004720:Endonucleases D006801:Humans D007251:Influenza, Human D009025:Morpholines D009975:Orthomyxoviridae D011728:Pyridones D012324:RNA-Dependent RNA Polymerase D014227:Triazines D014764:Viral Proteins D014779:Virus Replication
endonuclease Influenza antivirals neuraminidase polymerase pandemic hemagglutinin resistance.