Investigation of in vitro antiviral and antimicrobial activities of cepharanthine-luteolin and their interaction with pepsin by multispectral and molecular docking methods

• Published in: Journal of molecular liquids 2024-10, Vol.411, p.125811, Article 125811
• Main Authors: Zhang, Qian, Li, Mingyuan, Liu, Cui, Li, Yutong, Guo, Yu, Jiang, Hanlu, Liu, Jie, Hong, Min
• Format: Article
• Language: English
• Subjects: Anti-SARS-CoV-2; Cepharanthine; Luteolin; Pepsin
• ISSN: 0167-7322
• DOI: 10.1016/j.molliq.2024.125811

•Combination of CEP and Lut shows synergism without antagonism.•Ingestion of CEP before Lut is more conducive to the efficient utilization of drugs.•Inhibition mechanism of CEP and Lut on Pep is non-competitive. The antimicrobial, anticancer, and anti-SARS-CoV-2 activities of cepharanthine (CEP) combined with luteolin (Lut) were compared and analyzed by in vitro bioactivity experiment and molecular docking. CEP shows stronger biological activity than Lut, and their combination shows synergism without antagonism, especially in the fungal inhibition and anticancer activity experiments. It is believed that the antiviral activity is still effective confirmed by the simulation between two drugs and anti-SARS-CoV-2. Further, pepsin (Pep) was chosen for imitative gastroenteric environments to study its protease activity and structure effected by two drugs. The results show that the inhibitory mechanism of Lut/CEP is non-competitive inhibition, the binding mechanism is static quenching driven by enthalpy, the order of drug addition can affect the strength of binding ability, and the strength of binding ability is positively correlated with the inhibitory effect on enzyme activity. The ingestion of CEP before ingestion of Lut is more conducive to the efficient utilization of them. Their combination can not only decrease the dosage and toxicity, but also enhance the anti-inflammatory and anti-virus effects. These results can provide theoretical support for the development and utilization of Lut and CEP, and may supply one of the treatment for deal with the newly appeared viruses.