Why is the South African SARS-CoV-2 Strain Spreading Fast

ImmunityBio Inc study found mutation E484K results in very high affinity binding
medical laboratory
California (Precision Vaccinations News)

A privately-held, California based immunotherapy company announced their findings from a follow-up Molecular Dynamics (MD) simulation study of the SARS-CoV-2 spike receptor-binding domain (RBD) and its binding to its receptor on human cells, angiotensin-converting enzyme 2 (ACE2).

ImmunityBio, Inc. reported in the non-peer-reviewed study, “Millisecond-scale molecular dynamics simulation of spike RBD structure reveals evolutionary adaption of SARS-CoV-2 to stably bind ACE2” using exceptionally long-duration millisecond scale MD simulation, scientists revealed the evolutionary adaptation of spike RBD for binding to ACE2, and the regions of RBD that strongly bind ACE2. These findings provide targets for potential new therapeutics or vaccines.

In the new study, MD simulation was applied to the highly concerning new strains of SARS-CoV-2, including the predominating variant in South Africa 501Y.V2 and the UK variant B.1.1.7. 

The simulations were focused on the mutations found at the interface of the spike RBD and ACE2, E484K, K417N, and N501Y because these mutations are highly likely to affect binding and thus transmissibility. Indeed, both E484K and N501Y were found to increase RBD binding affinity to ACE2.

A very notable finding of the MD simulations was that the combination of E484K, K417N, and N501Y, found only in the South African variant, results in the highest degree of conformational alterations of S RBD when bound to hACE2, compared to either E484K or N501Y alone.

‘Enhanced affinity of S RBD for hACE2 very likely underpins the greater transmissibility conferred by the presence of E484K or N501Y. In comparison, the induction of conformational changes may explain evidence that the 501Y.V2 variant, distinguished from the B.1.1.7 UK variant by the presence of E484K, can escape neutralization by existing first-wave anti-SARS-CoV-2 antibodies and re-infect COVID-19 convalescent individuals.

The manuscript is available on preprint server bioRxiv and is concurrently undergoing scientific peer-review for publication.

The study authors have declared no competing interest.

ImmunityBio, Inc. is a late-clinical-stage immunotherapy company developing next-generation therapies that drive immunogenic mechanisms for defeating cancers and infectious diseases.

PrecisionVaccinations publishes research-based vaccine news.

 

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