tetano
Editor, Senior Moderator
Comb Chem High Throughput Screen
. 2022 Jun 7.
doi: 10.2174/1386207325666220607145225. Online ahead of print.
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
Anwar Mohammad[SUP] 1 [/SUP], Jehad Abubaker[SUP] 1 [/SUP], Fahd Al-Mulla[SUP] 2 [/SUP]
Affiliations
Abstract
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. As such, 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 acids substitutions on the S-protein and utilised 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 demonstrate that the S-protein of both variants possesses higher binding affinity to ACE2 than WT, with the South African 501Y.V2 is a more infective strain 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.
Keywords: 501Y.V2; B.1.1.7; SARS-CoV-2; new variant; protein-protein docking.
. 2022 Jun 7.
doi: 10.2174/1386207325666220607145225. Online ahead of print.
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
Anwar Mohammad[SUP] 1 [/SUP], Jehad Abubaker[SUP] 1 [/SUP], Fahd Al-Mulla[SUP] 2 [/SUP]
Affiliations
- PMID: 35674297
- DOI: 10.2174/1386207325666220607145225
Abstract
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. As such, 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 acids substitutions on the S-protein and utilised 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 demonstrate that the S-protein of both variants possesses higher binding affinity to ACE2 than WT, with the South African 501Y.V2 is a more infective strain 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.
Keywords: 501Y.V2; B.1.1.7; SARS-CoV-2; new variant; protein-protein docking.