Evaluation of Baloxavir Marboxil and Peramivir for the Treatment of High Pathogenicity Avian Influenza in Chickens

Abstract

Control measures in the case of high pathogenicity avian influenza (HPAI) outbreaks in poultry include culling, surveillance, and biosecurity; wild birds in captivity may also be culled, although some rare bird species should be rescued for conservation. In this study, two anti-influenza drugs, baloxavir marboxil (BXM) and peramivir (PR), used in humans, were examined in treating HPAI in birds, using chickens as a model. Chickens were infected with H5N6 HPAI virus and were treated immediately or 24 h from challenge with 20 mg/kg BXM or PR twice a day for five days. As per our findings, BXM significantly reduced virus replication in organs and provided full protection to chickens compared with that induced by PR. In the 24-h-delayed treatment, neither drug completely inhibited virus replication nor ensured the survival of infected chickens. A single administration of 2.5 mg/kg of BXM was determined as the minimum dose required to fully protect chickens from HPAI virus; the concentration of baloxavir acid, the active form of BXM, in chicken blood at this dose was sufficient for a 48 h antiviral effect post-administration. Thus, these data can be a starting point for the use of BXM and PR in treating captive wild birds infected with HPAI virus.

Medicinal Chemistry Gone Wild

“…Antiviral treatment, for instance with drugs 1 – 3 (Figure A), is not currently an option, and sick raptors brought to rehabilitation centers will receive supportive care, but few will survive. A single dose of baloxavir marboxil ( 3 ) has shown promise, outperforming peramivir ( 2 ), in clearing highly pathogenic avian influenza in chickens ( Gallus gallus domesticus ) . However, the treatment of raptors, captive or wild, with our precious contemporary arsenal of antivirals could lead to drug-resistant viral strains that would then present a zoonotic threat to humans.…”

“…A single dose of baloxavir marboxil (3) has shown promise, outperforming peramivir (2), in clearing highly pathogenic avian influenza in chickens (Gallus gallus domesticus). 9 However, the treatment of raptors, captive or wild, with our precious contemporary arsenal of antivirals could lead to drug-resistant viral strains that would then present a zoonotic threat to humans. For this reason, the FDA has banned the use of the antiviral oseltamivir (1) in poultry.…”

Antiviral Chemotherapy in Avian Medicine—A Review

“…BXM shows antiviral activity against H5 highly pathogenic avian influenza strains [ 9 , 79 ]. In chickens infected with the H5N6 HPAI virus, a single administration of 2.5 mg/kg BW of BXM immediately after inoculation was determined as the minimum dose required to fully protect chickens from the HPAI virus [ 80 ]. The concentration of baloxavir acid, the active form of BXM, in chicken blood at this dose was sufficient for a 48 h antiviral effect post-administration.…”

Influenza antivirals and animal models

“…Due to the relevance of chickens for IAV, few antivirals have been evaluated in this model against HPAI. BXM and peramivir showed to be effective against H5N6 reducing viral titers and mortality when chickens are immediately treated after the challenge [161]. In the case of H9N2, positive results have been observed with oseltamivir upon challenge with IAV H9N2 or Taishan Pinus massoniana pollen polysaccharides reducing viral loads and histopathological lesions [162,163].…”