A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike

Xia, Shuai; Yan, Lei; Xu, Wei; Agrawal, Anurodh Shankar; Algaissi, Abdullah; Tseng, Chien-Te K.; Wang, Qian; Du, Lanying; Tan, Wenjie; Wilson, Ian A.; Jiang, Shibo; Yang, Bei; Lu, Lu

In vivo safety of EK1 through intranasal administration As previously described (27) , female Balb/c mice (8 weeks old) were assigned randomly to three groups (n = 5) and continuously administered with PBS, low-dose EK1 (20 mg/kg), or high-dose EK1 (100 mg/kg) by intranasal route every day for 1 week. The body weight changes were monitored for the following 2 weeks. ALT and creatinine in the sera of each group of mice were measured using the ALT and creatinine assay kits (NJJCBIO, Nanjing, China) before the first treatment and 1, 3, and 5 days after the final treatment. The titer of immunoglobulin G sera to EK1 in each group of mice was evaluated by ELISA 2 weeks after the final treatment. Four weeks after administration, mice in each group mice were euthanized to harvest the lungs, livers, kidneys, and spleens for hematoxylin and eosin staining. The animal studies were approved by the Institutional Laboratory Animal Care and Use Committee at Fudan University (20180302-019).