South African (501Y.V2) and the United Kingdom (B.1.1.7) SARS-CoV-2 Spike (S) Protein Variants Demonstrate a Higher Binding Affinity to ACE2.

INTRODUCTION

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the lower respiratory tract by binding to angiotensin-converting enzyme 2 (ACE2) via its S-protein. Recent emerging SARS-CoV-2 variants from the United Kingdom (B.1.1.7) and South Africa (501Y.V2) are spreading worldwide at an alarming rate. The new variants have manifested amino acid substitution K417N, E484K, and N501Y on the RBD domain that binds to ACE2. These mutations may influence the binding of the S-protein to ACE2 and affect viral entry into the host cell.

METHODS

In this study, we modelled the amino acid substitutions on the S-protein and utilised the HADDOCK server to assess the S-protein RBD domain binding with ACE2. Additionally, we calculated the binding affinity of ACE2 to S-protein WT, B.1.1.7 and 501Y.V2 variants using Molecular Mechanics-Generalized Born Surface Area (MM/GBSA).

RESULTS

We demonstrated that the S-protein of both variants possesses a higher binding affinity to ACE2 than WT, with the South African 501Y.V2 being more infective than the B.1.1.7 that originated in the United Kingdom.

CONCLUSION

The South African 501Y.V2 variant presents three amino acid substitutions that changed the H-bonding network, resulting in a higher affinity to ACE2, indicating that the 501Y.V2 strain is more infective than the B.1.1.7 strain.