Recombinant SARS-CoV-2, RBD Protein (Alpha, B1.1.7, UK Variant)

This alpha variant of SARS-CoV-2 (also known as 20I/501Y.V1, VOC 202012/01, or B.1.1.7) emerged in the United Kingdom (UK) with a large number of mutations.

This variant has been detected in numerous countries, including the United States.1 The RBD mutation is N501Y, A570D. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is an enveloped, single-stranded, positive-sense RNA virus that belongs to the Coronaviridae family 2.

The SARS-CoV-2 genome, which shares 79.6% identity with SARS-CoV, encodes four essential structural proteins: the spike (S), envelope (E), membrane (M), and nucleocapsid protein (N) 3.

The S protein is a transmembrane, homotrimeric, class I fusion glycoprotein that mediates viral attachment, fusion, and entry into host cells 4.

Each ~180 kDa monomer contains two functional subunits, S1 (~700 a.a) and S2 (~600 a.a), that mediate viral attachment and membrane fusion, respectively.

S1 contains two major domains, the N-terminal (NTD) and C-terminal domains (CTD).

The CTD contains the receptor-binding domain (RBD), which binds to the angiotensin-converting enzyme 2 (ACE2) receptor on host cells 4-6.

Although both SARS-CoV and SARS-CoV-2 bind the ACE2 receptor, the RBDs only share ~73% amino acid identity, and the SARS-CoV-2 RBD binds with a higher affinity compared to SARS-CoV 4,7.

The RBD is dynamic and undergoes hinge-like conformational changes, referred to as the “down” or “up” conformations, which hide or expose the receptor-binding motifs, respectively 8.

Following receptor binding, S1 destabilizes, and TMPRSS2 cleaves S2, which undergoes a pre- to post-fusion conformation transition, allowing for membrane fusion 9,10.