Abstract: Objective To observe the effect of preventive administration of Qingjie Fanggan Granules on this disease-model combination, and explore its possible role in COVID-19 by establishing a mouse model of human coronavirus 229E infection with dampness-heat pestilential toxin attacking the lung, which simulates the TCM syndromes of COVID-19 infection. Methods Sixty BALB/C mice were randomly divided into normal control group, dampness-toxin control group, dampness-heat control group, virus control group, and high/low dose groups of Qingjie Fanggan Granules (8.2/4.1 g·kg^-1·d^-1). The syndrome-combined model of human coronavirus 229E was established by modeling mice with a damp-heat environment and intranasal infection of 229E. The administration groups were given the drug starting from when the mice were placed in the damp-heat environment until before 229E virus infection. Mice were sacrificed 1 day after 229E virus infection, and lungs and spleens were harvested. Calculate lung and spleen indices, lung inhibition rate. Detect viral load in lung tissues by RT-PCR, observe pathological changes of lung and spleen. Detect levels of inflammatory factors IL-6, TNF-α, IL-1β and IL-8 in lung tissues by ELISA. Detect expressions of P-p38 and p38 proteins in p38 MAPK signaling pathway of lung tissues by Western Blot. Results Compared with the dampness-toxin control group, Qingjie Fanggan Granules significantly reduced the lung index (P<0.01) and increased the spleen index (P<0.05) in mice with damp-heat pestilential toxin attacking the lung infected by human coronavirus 229E. The lung index inhibition rates of high and low-dose groups were 61.73% and 71.15% respectively. It could significantly reduce the viral load in lung tissues (P<0.01), alleviate lung tissue lesions (P<0.01 or P<0.05), improve splenic tissue pathological changes, and significantly decrease the levels of IL-6, TNF-α, IL-1β and IL-8 in lung tissues (P<0.01 or P<0.05), as well as the expression of P-p38 protein in the MAPK pathway (P<0.05). Conclusion Preventive administration of Qingjie Fanggan Granules can alleviate lung inflammation caused by HCoV-229E infection, and its mechanism may be related to the inhibition of p38 protein phosphorylation and the MAPK signaling pathway.

Key words: Qingjie Fanggan Granules, Coronavirus, Preventive Effect, Combination of Disease and Syndrome, Inflammatory Factor, p38, MAPK Signaling Pathway, Mice