Abstract
SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells. It has been reported that the UK and South African strains may have higher transmission capabilities, eventually due to amino acid substitutions on the SARS-CoV-2 Spike protein. The pathogenicity seems modified but is still under investigation. Here we used the experimental structure of the Spike RBD domain co-crystallized with part of the ACE2 receptor and several in silico methods to analyze the possible impacts of three amino acid replacements (Spike K417N, E484K, N501Y) with regard to ACE2 binding. We found that the N501Y replacement in this region of the interface (present in both UK and South African strains) should be favorable for the interaction with ACE2 while the K417N and E484K substitutions (South African) would seem unfavorable. It is unclear if the N501Y substitution in the South African strain could counterbalance the predicted less favorable (regarding binding) K417N and E484K Spike replacements. Our finding suggests that, if indeed the South African strain has a high transmission level, this could be due to the N501Y replacement and/or to substitutions in regions outside the direct Spike-ACE2 interface.
Hihglights
Transmission of the UK and possibly South African SARS-CoV-2 strains appears substantially increased compared to other variants
This could be due, in part, to increased affinity between the variant Spike proteins and ACE2
We investigated in silico the 3D structure of the Spike-ACE2 complex with a focus on Spike K417N, E484K and N501Y
The N501Y substitution is predicted to increase the affinity toward ACE2 (UK strain) with subsequent enhanced transmissibility and possibly pathogenicity
Additional substitutions at positions 417 and 484 (South African strain) may pertub the interaction with ACE2 raising questions about transmissibility and pathogenicity
Competing Interest Statement
The authors have declared no competing interest.
