Dry extract BNO 1011 inhibits human influenza a replication and neuraminidase activity in oseltamivir-resistant and -sensitive viral strains

Background

Virus infection is the main triggering event for the development of acute rhinosinusitis and human influenza A virus ranks among the most frequent viral causes of infection. Influenza neuraminidase, a key enzyme in viral replication, spread, and pathogenesis, is the primary target in prevention and treatment of influenza infection. Sinupret^®, a herbal medicinal product composed of Gentianae radix, Primulae flos, Sambuci flos, Rumicis herba, and Verbenae herba, is frequently used for the treatment of acute rhinosinusitis.

Objective

To investigate the anti-viral activity of the Sinupret^® dry extract BNO 1011 in vitro and its potential to inhibit neuraminidase in oseltamivir-resistant and -sensitive human influenza A H1N1 strains of clinical relevance.

Methodology

In vitro, BNO 1011 was tested for its interference with human influenza A infection using a plaque reduction assay in MDCK cells. The impact on two clinically relevant human influenza A H1N1 strains displaying divergent sensitivity against the well-known neuraminidase inhibitor oseltamivir (OS) was studied (OS-sensitive: human influenza A/California/07/2009; OS-resistant: human influenza A/Maryland/04/2011). In addition, BNO 1011 was studied for its inhibitory activity on neuraminidase of the same influenza A strains in a highly sensitive chemiluminescence assay. The in vitro experiments were paralleled by monitoring viability of MDCK cells in the presence of BNO 1011.

Results and conclusions

BNO 1011 efficiently blocked the infectivity of both influenza A H1N1 strains studied in a plaque reduction assay [EC₅₀: 8.3 µg/mL (A/California/07/2009), 8.2 µg/mL (A/Maryland/04/2011)] but did not affect cell viability (CC₅₀>1 mg/mL), yielding a therapeutic index (CC₅₀/EC₅₀) of 121 and 122, respectively. BNO 1011 also inhibited neuraminidase activity in both viral strains with comparable efficiency [IC₅₀: 59.3 µg/mL (A/California/07/2009), 99.7 µg/mL (A/Maryland/04/2011)], irrespective of the strains' oseltamivir sensitivity. Taken together, Sinupret^® dry extract BNO 1011 inhibits the replication of clinically relevant influenza A isolates. As underlying mechanism, the inhibition of viral neuraminidase was identified. Our results support the application of Sinupret^® dry extract BNO 1011 in the treatment of acute, viral rhinosinusitis.