Influenza virus polymerase inhibitors in clinical development.

Article Details

Citation

Hayden FG, Shindo N

Influenza virus polymerase inhibitors in clinical development.

Curr Opin Infect Dis. 2019 Apr;32(2):176-186. doi: 10.1097/QCO.0000000000000532.

PubMed ID
30724789 [ View in PubMed
]
Abstract

PURPOSE OF REVIEW: We review antivirals inhibiting subunits of the influenza polymerase complex that are advancing in clinical development. RECENT FINDINGS: Favipiravir, pimodivir, and baloxavir are inhibitory in preclinical models for influenza A viruses, including pandemic threat viruses and those resistant to currently approved antivirals, and two (favipiravir and baloxavir) also inhibit influenza B viruses. All are orally administered, although the dosing regimens vary. The polymerase basic protein 1 transcriptase inhibitor favipiravir has shown inconsistent clinical effects in uncomplicated influenza, and is teratogenic effects in multiple species, contraindicating its use in pregnancy. The polymerase basic protein 2 cap-binding inhibitor pimodivir displays antiviral effects alone and in combination with oseltamivir in uncomplicated influenza, although variants with reduced susceptibility emerge frequently during monotherapy. Single doses of the polymerase acidic protein cap-dependent endonuclease inhibitor baloxavir are effective in alleviating symptoms and rapidly inhibiting viral replication in otherwise healthy and higher risk patients with acute influenza, although variants with reduced susceptibility emerge frequently during monotherapy. Combinations of newer polymerase inhibitors with neuraminidase inhibitors show synergy in preclinical models and are currently undergoing clinical testing in hospitalized patients. SUMMARY: These new polymerase inhibitors promise to add to the clinical management options and overall control strategies for influenza virus infections.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
FavipiravirRNA-directed RNA polymerase catalytic subunitProteinInfluenza A virus (strain A/Silky Chicken/Hong Kong/SF189/2001 H5N1 genotype A)
Yes
Not AvailableDetails
Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
FavipiravirAldehyde oxidaseProteinHumans
No
Substrate
Inhibitor
Details
FavipiravirCytochrome P450 2C8ProteinHumans
Unknown
Inhibitor
Details
FavipiravirXanthine dehydrogenase/oxidaseProteinHumans
No
Substrate
Details