Screening and mechanism study on SARS-CoV-2 Mpro inhibitory of peptides from Spirulina platensis

Abstract In this study, four kinds of Spirulina platensis ( S. platensis) peptides were obtained by enzymolysis of protein after different pretreatment to S. platensis powders. The novel coronavirus main protease (SARS-CoV-2 main protease, Mpro) was successfully prepared by heterologous expression in E. coli and its activity was detected. After identification of S. platensis peptides sequences, highly active peptides were synthesized and their inhibition effects on Mpro was verified. Subsequnently, the mechanism of action between them were analyzed by computer simulations. Results showed that the extraction rate of the protein from S. platensis was 96.11%, the activity of Mpro was 845.90 U mg-1, the peptide MQGPNY could inhibit the activity of Mpro with the inhibition rate of 20.21%±3.8% at the concentration of 2 mM. Fuerthermore, results from computer Simulation showed that the peptide MQGPNY forms four pairs of hydrogen bonds with Mpro, which are Gln189, Ser46, Thr26 and Glu166. In addition, there were nine free residues involved in hydrophobic contacts, which were His164, His41, Thr24, Met49, Thr45, Thr25, Gly143, Asn142, and Cys145 and Met165. This study developed natural peptides from S. platensis, which could inhibited the activity of Mpro. Besides, the mechanism of the peptide MQGPN acting on Mpro was revealed by the method of computer Simulation. The foundings could provide theoretical support for the use of protein and its hydrolysates from S. platensis in functional food and supplement formulations in the post-epidemic era.