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At Montana Molecular, we are committed to developing validated tools and services to support COVID-19 drug discovery.

2nd generation pseudoviruses for SARS-CoV-2 variants are on the way.

Emerging SARS CoV-2 Variants

In the spring of 2020, Manaus Brazil, was hit hard by the Coronavirus. The disease was widespread, and it appeared that nearly 75% of the population was infected at some point during that early outbreak. Now, a resurgence of COVID in Manaus suggests that a new variant is re-infecting residents who survived the disease a mere 10 months ago. The new variant, known as P.1, shares similarities with rapidly spreading new variants isolated in South Africa (B.1.1.7) and England (B.1.351). Analysis of these variants suggest that the key mutations of concern are examples of convergent evolution.  

Mutations of Concern in the Spike Protein

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. This mutation is found in all three variants of the virus. 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.

 

On the Lookout: Other Changes in SARS CoV-2

The mutations shared by all three of the current highly transmissible variants are notable because they arose independently, but each lineage also contains unique changes in the Spike protein that may prove to be functionally important as well. For example, the deletion of amino acids 69/70 in B.1.1.7 has occurred in several different lineages of the virus independently, and the P681H mutation in the B.1.1.7 lineage is adjacent to the furin cleavage site which is presumably important in the Spike protein function because of it’s location.

Which screening strategy would you prefer for testing potential neutralizing antibodies or blocking agents?
    • Pseudovirus D614G K417N E484K N501Y- The spike protein is the D614G strain with additional mutations at K417N, E484K, and N501Y.
    • Multiple real world pseudovirus variants, each with the complete suite of spike protein mutations for each strain, e.g. P.1, B.1.351, B.1.1.7.

Resources for SARS CoV-2 Research

Please send comments and questions about our new pseudovirus variants to [email protected]