SARS-CoV-2 Mutants Protein

Genetic variants of SARS-CoV-2 have been emerging and circulating around the world throughout the COVID-19 pandemic. The U.K. variant B.1.1.7, the Brazil variant P.1, the South Africa variant B.1.351, and the most recent Indian variant B.1.617 are particular concerning because of their high prevalence.

While the Spike protein in each variant has several mutations, there are three that are of particular concern. The N501Y mutation occurs in the receptor binding domain of the spike protein, positioned to influence binding to the host ACE2 receptor. The E484K mutation is found in both the South African strain (B.1.1.7) and the one that is now prevalent in Brazil (P.1). There is growing evidence that this mutation may diminish neutralizing effects of some antibodies. K417 has mutated to N in the B.1.351 lineage, while it changed to T (K417T) in the P1 lineage identified in Brazil.

The mutations in these strains also occur in the nucleocapsid protein, which is commonly used as the biomarker in rapid antigen tests. It's critical to assess whether the current commercial antigen tests can detect the mutated N proteins with the same sensitivity and specificity as their WT counterpart.

Creative Diagnostics are going full steam ahead on developing a collection of recombinant antigens for these variants, including Spike proteins and Nucleocapsid proteins, covering critical mutations such as K417N/T, E484K, N501Y and D614G on Spike protein and R203G, G204R and P13L on Nucleocapsid protein. The reagents can be used to evaluate the efficacy of the antibodies and vaccination.