Abstract: After the outbreak of SARS-CoV-2, more and more mutants with stronger infectivity appeared. The most representative strains were B.1.351 and B.1.617, which had a common feature of amino acid mutation at spike protein 484 site. Site 484 is a site where interacts with residue K31 on hACE2. From the perspective of molecular dynamics and protein docking, E484K and E484Q mutations of SARS-CoV-2 were investigated, and it was found that the hydrogen bonds between amino acid residues (A475 and N489) that directly interact with hACE2 were shortened due to 484 mutations. Kinetic results also showed that amino acid sequence 475-489 was highly active and should not be neglected as drug design targets. It can provide a new target for the development of SARS-CoV-2 inhibitors, predict the future evolutionary direction of SARS-CoV-2 to a certain extent, and also provide a new idea for the mutation research of similar coronavirus.

Key words: SARS-CoV-2, spike protein, RBD, hACE2, molecular dynamics simulation