Potential Role of Endonuclease Inhibition and Other Targets in the Treatment of Influenza

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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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:21

Enthalten in:

Current drug targets - 21(2020), 2 vom: 01., Seite 202-211

Sprache:

Englisch

Beteiligte Personen:

Szollosi, Doreen [VerfasserIn]
Bill, Ashley [VerfasserIn]

Links:

Volltext

Themen:

4G86Y4JT3F
Antiviral Agents
Antivirals
Baloxavir
Dibenzothiepins
EC 2.7.7.48
EC 3.1.-
Endonuclease
Endonucleases
Hemagglutinin
Influenza
Journal Article
Morpholines
Neuraminidase
Pandemic
Polymerase
Pyridones
RNA-Dependent RNA Polymerase
Resistance.
Review
Triazines
Viral Proteins

Anmerkungen:

Date Completed 02.02.2021

Date Revised 02.02.2021

published: Print

Citation Status MEDLINE

doi:

10.2174/1389450120666190801115130

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM299803090