SARS-CoV-2 RBD of Spike protein N501Y – B 1.1.7 lineage – UK Variant

The N501Y mutation in the receptor-binding domain (RBD) has been detected in an emerging variant of SARS-CoV-2. The variant, known as lineage B.1.1.7, Variant of Concern (VOC) 202012/01 or clade 20B / 501Y.V1, was first discovered in Kent, United Kingdom (UK), in mid-September 2020 and its frequency and distribution continued to grow ever since.

The growing number of infections caused by this variant of the new coronavirus has raised cause for concern. The N501Y mutation is found at one of six key residues within RBD and has been linked to an improved binding affinity for human ACE2 (angiotensin-converting enzyme 2). The improvement may also explain the rapid expansion of its geographic distribution and potentially higher infectivity compared to other variants of the COVID-19 virus.

Aside from the N501Y mutation, the B.1.1.7 lineage has accumulated 16 additional non-synonymous mutations and deletions within the peak protein (but outside the 320-541 region). The most concerning besides the N501Y include:

The 69-70del in the N-terminal domain of the peak, which has previously been linked to an improved ability to evade the human immune system.

The P681H mutation is adjacent to the spike furin cleavage site, a location of high biological importance due to its role in spike cleavage and the membrane fusion process.

It is hypothesized that these cumulative mutations contribute to increased infectivity and rapid spread of the B.1.1.7 lineage. However, it is not yet clear whether this large number of changes in the peak will affect the severity of the disease or even hamper the efficiency of current COVID-19 vaccines.

69-70del has also been a cause of difficulty in effective RT-PCR detection kits that target the SARS-CoV-2 spike protein. This has created the need to develop a new assay that allows accurate surveillance of variant B.1.1.7. Additionally, more studies are needed to elucidate the impact of this set of mutations on the progression of COVID-19 disease.

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