Additional file 1: of Sheng Jiang San, a traditional multi-herb formulation, exerts anti-influenza effects in vitro and in vivo via neuraminidase inhibition and immune regulation

Method of High-performance liquid chromatography (HPLC) analysis of SJS. HPLC method was used to analyze the chemical profile of SJS. The HPLC condition is described in this additional file and the profile is shown in Additional file 2: Figure S1. By comparing with reference compounds, rhein, chrysophanol, emodin, aloe emodin and curcumin were found. (DOCX 13 kb

Additional file 2: of Sheng Jiang San, a traditional multi-herb formulation, exerts anti-influenza effects in vitro and in vivo via neuraminidase inhibition and immune regulation

Figure S1. HPLC analysis of SJS (a) HPLC profile of SJS (b) Some constituents were denoted by standard compounds. (PPTX 128 kb

Discovery of Highly Potent Pinanamine-Based Inhibitors against Amantadine- and Oseltamivir-Resistant Influenza A Viruses

Influenza pandemic is a constant major threat to public health caused by influenza A viruses (IAVs). IAVs are subcategorized by the surface proteins hemagglutinin (HA) and neuraminidase (NA), in which they are both essential targets for drug discovery. While it is of great concern that NA inhibitor oseltamivir resistant strains are frequently identified from human or avian influenza virus, structural and functional characterization of influenza HA has raised hopes for new antiviral therapies. In this study, we explored a structure–activity relationship (SAR) of pinanamine-based antivirals and discovered a potent inhibitor <b>M090</b> against amantadine-resistant viruses, including the 2009 H1N1 pandemic strains, and oseltamivir-resistant viruses. Mechanism of action studies, particularly hemolysis inhibition, indicated that <b>M090</b> targets influenza HA and it occupied a highly conserved pocket of the HA₂ domain and inhibited virus-mediated membrane fusion by “locking” the bending state of HA₂ during the conformational rearrangement process. This work provides new binding sites within the HA protein and indicates that this pocket may be a promising target for broad-spectrum anti-influenza A drug design and development

Discovery of Highly Potent Pinanamine-Based Inhibitors against Amantadine- and Oseltamivir-Resistant Influenza A Viruses

Influenza pandemic is a constant major threat to public health caused by influenza A viruses (IAVs). IAVs are subcategorized by the surface proteins hemagglutinin (HA) and neuraminidase (NA), in which they are both essential targets for drug discovery. While it is of great concern that NA inhibitor oseltamivir resistant strains are frequently identified from human or avian influenza virus, structural and functional characterization of influenza HA has raised hopes for new antiviral therapies. In this study, we explored a structure–activity relationship (SAR) of pinanamine-based antivirals and discovered a potent inhibitor <b>M090</b> against amantadine-resistant viruses, including the 2009 H1N1 pandemic strains, and oseltamivir-resistant viruses. Mechanism of action studies, particularly hemolysis inhibition, indicated that <b>M090</b> targets influenza HA and it occupied a highly conserved pocket of the HA₂ domain and inhibited virus-mediated membrane fusion by “locking” the bending state of HA₂ during the conformational rearrangement process. This work provides new binding sites within the HA protein and indicates that this pocket may be a promising target for broad-spectrum anti-influenza A drug design and development