New influenza virus polymerase inhibitors, including favipiravir, pimodivir, and baloxavir, demonstrate efficacy against strains resistant to current antivirals and synergy with neuraminidase inhibitors.
Do influenza virus polymerase inhibitors improve clinical outcomes and inhibit viral replication in patients with influenza?
New influenza polymerase inhibitors offer promising additions to clinical management, though challenges such as teratogenicity and resistance emergence highlight the potential need for combination therapies.
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.
Hayden et al. (Wed,) conducted a review in Influenza virus infections. Influenza virus polymerase inhibitors (favipiravir, pimodivir, baloxavir) was evaluated. New influenza virus polymerase inhibitors, including favipiravir, pimodivir, and baloxavir, demonstrate efficacy against strains resistant to current antivirals and synergy with neuraminidase inhibitors.