Dynamic Ca2+ sensitivity stimulates the evolved SARS-CoV-2 spike strain-mediated membrane fusion for enhanced entry.
Cell Rep
; 39(3): 110694, 2022 04 19.
Article
in English
| MEDLINE | ID: covidwho-1778029
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
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
SARS-CoV-2
/
COVID-19
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Cell Rep
Year:
2022
Document Type:
Article
Affiliation country:
J.celrep.2022.110694
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