Los Alamos team opens door to allosteric COVID-19 countermeasures

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A SARS-CoV-2 spike mutation linked to locally dominant strains could become the basis for allosteric COVID-19 countermeasure development.

A Los Alamos National Laboratory team has identified a SARS-CoV-2 spike mutation linked to locally dominant strains that could become the basis of allosteric COVID-19 countermeasure development.

The majority of COVID-19 vaccine and antibody candidates focus on the SARS-CoV-2 spike because it is used by the virus to invade cells. The spike’s receptor-binding domain (RBD), which interacts with host cells, is a prime antigen for neutralizing antibodies and is also unlikely to mutate.

Other regions of the spike, however, are amenable to change.

In a preprint posted April 30 to bioRxiv, the Los Alamos scientists reported a SARS-CoV-2 spike mutation -- denoted D614G and located outside the RBD -- associated with strains that, after local introduction, have become the dominant strain in multiple places including England, the Netherlands, New York state and Australia.

However, when looking at COVID-19 patients in Sheffield, U.K., the researchers found no statistically significant link between the D614G mutation and hospitalization, and only found about a fourfold increase in viral RNA levels for D614G vs. wild-type spike strains.

Because genome detection is a proxy for ongoing infection, the higher RNA levels suggest, but don’t prove, a higher viral load. And while the high local prevalence of D614G SARS-CoV-2 strains could be the result of chance, another possibility is the mutation is advantageous to the virus.

While the computational study did not investigate how the mutation might benefit SARS-CoV-2, the authors suggested the D614G mutation may allosterically alter the spike RBD structure and thus change the dynamics of its interaction with host cells or promote molecular events that lead to viral fusion.

Further studies may reveal ways to allosterically manipulate the SARS-CoV-2 spike to block cellular infection.

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