In vitro and in vivo anti-HMPV activity of JH001 isolated from Chinese medicinal herbs

ABSTRACT

OBJECTIVE Human metapneumovirus（h MPV） is semblable to respiratory syncytial virus（RSV） which causes respiratory infections typically characterized by cough, runny nose, fever, and nasal congestion but sometimes progressing to bronchiolitis and pneumonia. Whereas, there is no corresponding drug to inhabit the virus. Studies of new compounds with potential anti-HMPV activity could produce clinical value. Chinese herbal medicine played a great role during COVID-19, therefore we choose some small molecular（JH001） extracted from botany to investigate therapeutic effect on h MPV and the underlying mechanisms. METHODS In this study, 16 HBE cells were used as a model to explore in vitro antiviral effect. Cytotoxicity assays were performed before the antiviral tests, cell viability of 16 HBE cells handled by different concentration of JH001 was estimated by Cell Counting Kit-8（CCK-8）. Then RT-q PCR, immunofluorescence, and flow cytometer were used to test the viral titer after cells infected with h MPV. Eventually, 6-8 weeks mice were infected intranasally with 60 μL of h MPV, the control group was treated with 0.9% saline water, other groups were administered with JH001 and ribavirin, then the lung virus titer and protective effect in lung were judged. RESULTS The obtained JH001 exhibited no cytotoxicity to 16 HBE cells during 6.25-200 μmol · L-1. RT-QPCR demonstrated that JH001 showed obvious inhabitation to the viral replication and showed great significance compared with saline. And fluorescence exhibited distinct decrease of h MPV-N protein, flow cytometer results showed that MFI decrease evidently. Significant reduction of N-gene expression was observed in those mice treated with JH001 compared with saline group,which indicated that JH001 probably had protective and therapeutic effect on viral replication. CONCLUSION This study illustrated that JH001 might be a promising option for small molecular against h MPV and JH001 might be worthy of further development and used as a potential therapeutic strategy for other respiratory viruses in the future.