Spike Protein Potential Receptors Study: Comparative Computational Analysis Approach on SARS-CoV-2 -AC2/CD147 Complexes

SARS-CoV-2 invades host cells via interaction of its spike protein with the human angiotensin-converting enzyme 2 as the receptor. CD147, as a biomarker for hyperinflammation, was found to be the functional receptor for SARS-CoV-2 and an additional cell entry route. In this paper, we focused our analysis on the initial step of virus infection by comparing the affinity, stability, and specificity of the SARS-CoV-2 spike 1-AC2 and SARS-CoV-2 spike 1-CD147 complexes. Protein-protein docking was utilized for identifying the hotspot residues in the interface of spike protein with AC2 and CD147. The results of binding free energies showed a high affinity of SP1-AC2 complex (-52.97 kcal/mol) compared with SP1-CoV2/CD147 (-35.75 kcal/mol). RMSF values indicate that the spike protein of SARS-CoV-2 RBD is more compatible with binding to the human ACE2 with high flexibility. Computational analysis of binding modes and protein contacts reported that CD147 and ACE2 might be two complementary receptors mediating virus infection and confirmed the experimental results previously.