Viruses, Vol. 12, Pages 1139: In Vitro Combinations of Baloxavir Acid and Other Inhibitors against Seasonal Influenza A Viruses

Viruses, Vol. 12, Pages 1139: In Vitro Combinations of Baloxavir Acid and Other Inhibitors against Seasonal Influenza A Viruses Viruses doi: 10.3390/v12101139 Authors: Liva Checkmahomed Blandine Padey Andrés Pizzorno Olivier Terrier Manuel Rosa-Calatrava Yacine Abed Mariana Baz Guy Boivin Two antiviral classes, the neuraminidase inhibitors (NAIs) and polymerase inhibitors (baloxavir marboxil and favipiravir) can be used to prevent and treat influenza infections during seasonal epidemics and pandemics. However, prolonged treatment may lead to the emergence of drug resistance. Therapeutic combinations constitute an alternative to prevent resistance and reduce antiviral doses. Therefore, we evaluated in vitro combinations of baloxavir acid (BXA) and other approved drugs against influenza A(H1N1)pdm09 and A(H3N2) subtypes. The determination of an effective concentration inhibiting virus cytopathic effects by 50% (EC50) for each drug and combination indexes (CIs) were based on cell viability. CompuSyn software was used to determine synergism, additivity or antagonism between drugs. Combinations of BXA and NAIs or favipiravir had synergistic effects on cell viability against the two influenza A subtypes. Those effects were confirmed using a physiological and predictive ex vivo reconstructed human airway epithelium model. On the other hand, the combination of BXA and ribavirin showed mixed results. Overall, BXA stands as a good candidate for combination with s...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research