Overview:

The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein recognizes the host ACE2 receptor and is a major determinant of viral entry and neutralization (1). SARS-CoV-2 (501Y.V2 variant) with mutations at the key sites in RBD (K417N, E484K and N501Y) has severely affected regions of South Africa (2). MD simulation indicates that the combination of E484K, K417N and N501Y results in the highest degree of conformational modifications of RBD when bound to hACE2, compared to either E484K or N501Y alone. E484K and N501Y increase affinity of RBD for hACE2 and the charge switch due to E484K leads to the formation of favorable contacts. As new variants displace the first-wave virus, it is pivotal to evaluate their transmissibility, virulence and their possible tendency to escape antibody neutralization (3).

Gene Aliases:

2019-nCoV RBD, SARS-CoV-2 spike RBD, novel coronavirus spike RBD, nCov spike RBD.

Genbank Number:

MN908947

References:

1. Lan J, et al: Crystal structure of the 2019-nCov spike receptor-binding domain bound with the ACE2 receptor. bioRxiv. doi: https://doi.org/10.1101/2020.02.19.956235.

2. Houriiyah T, et al: Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. medRxiv 2020; doi: https://doi.org/10.1101/2020.12.21.20248640

3. Starr TN, et al: Molecular dynamic simulation reveals E484K mutation enhances spike RBD-ACE2 affinity and the combination of E484K, K417N and N501Y mutations (501Y.V2 variant) induces conformational change greater than N501Y mutant alone, potentially resulting in an escape mutant. Cell. 2020, 182(5):1295-1310.