Structural Insights into How An Early SARS-Cov-2 Variant Gained its Advantage (Medicine)

In an analysis that explores the structural underpinnings of a SARS-CoV-2 strain, G614, that quickly became dominant early in the pandemic, researchers discovered interactions that prevent this strain’s spike from shedding its host binding domain too early. This may explain the enhanced infectivity of the G614 virus, they say. Throughout the COVID-19 pandemic, epidemiologists have monitored evolution of the SARS-CoV-2 virus with particular focus on the spike (S) protein. Spike trimers decorate the viral surface and facilitate host cell entry. An early variant with a single-residue substitution (G614) in its spike protein rapidly became the dominant strain throughout the world, and studies have also suggested it is more infectious than the original strain. Puzzlingly, studies have shown that it does not bind more tightly to recombinant ACE2, the host cell receptor. Jun Zhang et al. investigated the structural basis for the spread of the G614 virus. Structural and biochemical studies on a full-length G614 S trimer revealed interactions not present in D614, the original strain, which was described in a paper published in Science in July 2020. In particular, a loop wedges between domains in the G614 spike, in an added interaction that appears to stabilize the spike to prevent premature dissociation of the G614 trimer. This effectively increases the number of functional spikes. “[W]e suggest that the enhanced infectivity of the G614 virus largely results from the increased stability of the S trimer,” conclude the authors.

Reference: Yongfei Cai, Jun Zhang, Tianshu Xiao, Hanqin Peng, Sarah M. Sterling, Richard M. Walsh Jr., Shaun Rawson, Sophia Rits-Volloch, Bing Chen, “Distinct conformational states of SARS-CoV-2 spike protein”, Science  25 Sep 2020: Vol. 369, Issue 6511, pp. 1586-1592 DOI: 10.1126/science.abd4251

Provided by AAAS

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