Commentary Open Access
Volume 3 | Issue 2 | DOI: https://doi.org/10.33696/immunology.3.085

Structural Consequences of Variation in SARS-CoV-2 B.1.1.7

  • 1Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, USA
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Corresponding Author

David Ostrov, ostroda@pathology.ufl.edu

Received Date: February 06, 2021

Accepted Date: March 03, 2021


New globally circulating SARS-CoV-2 strains are causing concern about evolution of virus transmissibility, fitness and immune evasion mechanisms. A variant emerging from the United Kingdom called SARS-CoV-2 VUI 202012/01, or B.1.1.7, is thought to exhibit increased transmissibility that results from replication 4-10 times faster than the original Wuhan virus (Wuhan-Hu-1). Although this property is suspected to result from a specific mutation in the spike glycoprotein, D614G, there are 9 mutations that distinguish the UK variant B.1.1.7 from Wuhan-Hu-1 yet to be evaluated for functional effects. We asked if mutated positions fixed in UK variant B.1.1.7 may be involved in the virus life cycle, or evasion of the immune response, by modeling the UK variant spike protein and conducting structural analysis of mutations on the spike glycoprotein trimer (protomer) complexed to ACE2. Importantly, 4 out of 9 differences between the UK variant B.1.1.7 and Wuhan-Hu-1 spike protein alter direct intermolecular interactions. N501Y increased affinity between the spike protein and ACE2. The mutations at A570D, D614G and S982A reduced contact between individual chains of the trimeric spike protomer, potentially enhancing cleavage into S1 and S2 subunits, dynamic structural rearrangement and host cell fusion mechanisms. These data suggest that combined characteristics of mutations unique to UK variant B.1.1.7 enable high affinity binding to ACE2 and enhanced replication properties. The D614G mutation, associated with enhanced virus transmissibility, opens a potentially druggable structural pocket at the interface between spike glycoprotein subunits S1 and S2.



SARS-CoV-2; Angiotensin Converting Enzyme-2; Mutation; Drug discovery


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