Probenecid Inhibits Influenza A(H5N1) and A(H7N9) Viruses In Vitro and in Mice

Area of Science:

• Virology
• Infectious Diseases
• Pharmacology

Background:

• Avian influenza (AI) viruses, including highly pathogenic avian influenza (HPAI) H5N1 and H7N9 variants, pose significant threats to avian and human health.
• HPAI viruses have demonstrated high mortality rates in humans, underscoring the urgent need for effective antiviral therapies.
• Previous AI outbreaks since 1996 highlight the public health imperative for developing novel treatments.

Purpose of the Study:

• To investigate the antiviral potential of probenecid against HPAI H5N1 and H7N9 strains.
• To evaluate the efficacy of probenecid in both prophylactic and therapeutic settings in relevant cell and animal models.

Main Methods:

• In vitro antiviral assays using A549 and normal human broncho-epithelial (NHBE) cells treated with probenecid.
• In vivo studies involving H5N1-infected mice treated with probenecid.
• Replication inhibition assays in VeroE6 cells.

Main Results:

• Probenecid demonstrated potent inhibition of H5N1 and H7N9 replication in prophylactically and therapeutically treated A549 and NHBE cells.
• Probenecid also effectively inhibited H5N1 replication in VeroE6 cells and in a mouse model.
• These findings indicate broad-spectrum antiviral activity against tested HPAI strains.

Conclusions:

• Probenecid exhibits significant antiviral activity against HPAI H5N1 and H7N9.
• Probenecid represents a potential therapeutic candidate for managing avian influenza infections in humans.
• Further research into probenecid as an antiviral agent for HPAI is warranted.