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Cell Reports
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Dynamic Ca2+ sensitivity stimulates the evolved SARS-CoV-2 spike strain-mediated membrane fusion for enhanced entry

Authors: Singh, Puspangana; Mukherji, Shreya; Basak, Swarnendu; Hoffmann, Markus; Das, Dibyendu Kumar;

Dynamic Ca2+ sensitivity stimulates the evolved SARS-CoV-2 spike strain-mediated membrane fusion for enhanced entry

Abstract

Mutations in the spike protein generated a highly infectious and transmissible D614G variant, which is present in newly evolved fast-spreading variants. The D614G, Alpha, Beta, and Delta spike variants of SARS-CoV-2 appear to expedite membrane fusion process for entry, but the mechanism of spike-mediated fusion is unknown. Here, we reconstituted an in vitro pseudovirus-liposome fusion reaction and report that SARS-CoV-2 wild-type spike is a dynamic Ca2+ sensor, and D614G mutation enhances dynamic calcium sensitivity of spike protein for facilitating membrane fusion. This dynamic calcium sensitivity for fusion is found to be higher in Alpha and Beta variants and highest in Delta spike variant. We find that efficient fusion is dependent on Ca2+ concentration at low pH, and the fusion activity of spike dropped as the Ca2+ level rose beyond physiological levels. Thus, evolved spike variants may control the high fusion probability for entry by increasing Ca2+ sensing ability.

Keywords

SARS-CoV-2, Spike Glycoprotein, Coronavirus, COVID-19, Humans, Calcium, Membrane Fusion, Article

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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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    influence
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
32
Top 10%
Average
Top 1%
Green
gold