Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.06.09.730954

Evaluation of antiviral treatments for highly pathogenic avian influenza virus infections in feline species

Ishee, A. C.·Zhai, Z.·Oomens, M. J.·Collins, R. N.·Gomes Noll, J.·Whittaker, G. R.
View original source ↗Export metadata ↓

Abstract

In 2020, highly pathogenic avian influenza (HPAI) isolates from clade 2.3.4.4b emerged in Europe and spread globally, including in bovine hosts in the USA. Viruses from this clade cause minimal disease in dairy cattle, characterized by decreased milk production but low mortality rates. Infections have also occurred in feline hosts. In contrast to cows, infection of cats (and closely related species, including skunks and foxes) can result in severe neurological signs and mortality. Documented feline H5N1 infections from clade 2.3.4.4.b have a mortality rate of approximately 80% following rapid onset of clinical signs. No antiviral compounds have been tested in an experimental feline model; however, anecdotal clinical evidence suggests early treatment with oseltamivir may improve outcomes in felines with HPAI. Here, we show the in vitro efficacy of several influenza inhibitors in feline glial astrocyte (PG-4) and kidney (CRFK) cell culture models using the clade 2.3.4.4.b virus Tx2/24 (H5N1). The neuraminidase inhibitor oseltamivir carboxylate did not effectively inhibit viral replication in either cell line. The cap-dependent endonuclease inhibitor baloxavir exhibited the strongest inhibition of this virus, with EC50 values of 30 nM in PG-4 and 1 M in CRFK cells. Amantadine and rimantadine, M2 ion channel inhibitors, were unable to completely inhibit viral replication in either cell line at any concentration utilized. The broad-spectrum nucleoside analog GS-441524 demonstrated little to no inhibition of viral replication in either cell line. Additionally, the mutagenic NHC analogs EIDD-1931 and EIDD-2801 successfully inhibited viral replication at the maximum tested concentration of 100 M but exhibited significant cytotoxicity. Our findings suggest that baloxavir should be considered by veterinary clinicians as the first-line drug of choice when presented with felines or other species infected with HPAI.

Explore related subjects

microbiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Ishee, A. C., Zhai, Z., Oomens, M. J., Collins, R. N., Gomes Noll, J., Whittaker, G. R.. 2026-06-10. Evaluation of antiviral treatments for highly pathogenic avian influenza virus infections in feline species. https://doi.org/10.64898/2026.06.09.730954

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Extreme temperature exposure has negative demographic consequences for Sulfolobus acidocaldarius

Microorganisms inhabiting geothermal springs and volcanic systems experience fluctuating temperatures that can periodically exceed their upper thermal limits, but the demographic consequences of such exposure remain poorly understood. Here, we investigated demographic responses of the thermophilic archaeon Sulfolobus acidocaldarius to an extreme temperature (94.1{degrees}C) under two regimes: sustained exposure varying in duration, and episodic exposure interspersed with recovery at a permissive temperature (75{degrees}C). Under sustained exposure, populations showed no detectable loss of viability after 15 min but declined thereafter, decreasing by approximately five orders of magnitude after 120 min. Under episodic exposure, populations remained viable across nine exposure-recovery cycles but declined in density with successive cycles. Similar responses were observed for three strains, including a DNA mismatch repair knockout ({Delta}nucS), indicating that mismatch repair deficiency did not affect viability or recovery. Together, these results demonstrate that S. acidocaldarius can withstand brief and repeated exposure to near-boiling temperatures, with mortality determined primarily by cumulative exposure duration rather than a fixed thermal threshold.

microbiology↗
bioRxiv2026

Bacteriophage and Antibiotic Resistance Are Positively Associated across a Phylogenetically Diverse Set of Clinical Pseudomonas aeruginosa Isolates

Co-administration of phages and antibiotics has been proposed as a therapeutic approach against antibiotic-resistant bacteria. The relationship, however, between antibiotic resistance and phage resistance in clinical isolates is unclear. Here, we examine associations between phage and antibiotic resistance profiles across a panel of Pseudomonas aeruginosa clinical isolates from the Centers for Disease Control (CDC) and Food and Drug Administration (FDA) Antimicrobial Resistance Isolate (ARI) Bank comprising 55 clinical strains with full genome sequences and antibiotic susceptibility testing (AST) data for 11 clinically relevant antibiotics. As phages in this study, we use three well-characterized, morphologically distinct phages, OMKO1, Luz19, and PAML31-1. We screen for phage resistance using a growth suppression assay, then conduct statistical analysis against antibiotic MIC (Minimum Inhibitory Concentration) data provided by the CDC to define association patterns across this dataset. We find multiple significant susceptibility correlations between pairs of antibiotics and phages, and a positive overall association between average phage resistance and antibiotic resistance across the 55 strains, even controlling for phylogenetic associations (=0.358, p<0.005). We conclude that phage and antibiotic resistance are positively associated across this clinical isolate collection, suggesting that the two resistance phenotypes are not independent in P. aeruginosa. These findings have implications for the development of phage-antibiotic cocktails.

microbiology↗
bioRxiv2026

The Estuary Effect: Variations in Temperature and Salinity Alter msh Promoter Activity in Vibrio cholerae

Vibrio cholerae, the facultative pathogen underlying cholera, naturally inhabits warm aquatic estuaries. Environmental persistence is enhanced by the ability of V. cholerae to colonize host reservoirs and form multicellular biofilms, causing seasonally endemic outbreaks in many tropical regions. Most toxigenic strains utilize the type IVa mannose-sensitive hemagglutinin (MSHA) pilus for host reservoir colonization and biofilm formation. Temperature and salinity can alter V. cholerae biofilm formation, yet their impact on MSHA production specifically remains largely unknown. Here, we utilized transcriptional reporters of predicted msh promoters (msh-P1/msh-P2/msh-P3) and functional assays, to determine temperature and salinity impacts on msh expression and pilus biogenesis. Under standard laboratory conditions (30{degrees}C, 1% NaCl) only msh-P1/P2 are active and inversely-coordinated with one another. Both msh-P1/P2 activity were elevated by high temperature (37{degrees}C) and low salinity (0.25%/0.5% NaCl), and reduced by low temperature (20{degrees}C/25{degrees}C) and high salinity (2%/3% NaCl). Temperature-mediated alterations in promoter activity were not immediately reflected in changes to cell-surface MSHA levels, whereas high salinity led to decreased MSHA production. Combining high temperature (37{degrees}C) and high salinity (2%/3% NaCl), attenuated the salinity-mediated reduction of msh-P1/P2 activity. Biofilm biomass levels were only substantially heightened at 25{degrees}C and 20{degrees}C, likely a result of no temperature-dependent changes in cell-surface MSHA, and additional temperature-controlled biofilm regulation previously described. We also found msh-P1/P2 promoter activity and MSHA production varies widely across toxigenic O1 and O139 serogroups despite complete sequence homology. These results shed new light on how key signals regulate MSHA pilus production to support V. cholerae persistence in aquatic environments.

microbiology↗