Sarah Al-Beltagi
Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin
Al-Beltagi, Sarah; Goulding, Leah V.; Chang, Daniel K.E.; Mellits, Kenneth H.; Hayes, Christopher J.; Gershkovich, Pavel; Coleman, Christopher M.; Chang, Kin-Chow
Authors
Leah V. Goulding
Daniel K.E. Chang
KEN MELLITS KEN.MELLITS@NOTTINGHAM.AC.UK
Associate Professor
CHRIS HAYES chris.hayes@nottingham.ac.uk
Professor of Organic Chemistry
PAVEL GERSHKOVICH PAVEL.GERSHKOVICH@NOTTINGHAM.AC.UK
Associate Professor
CHRISTOPHER COLEMAN CHRISTOPHER.COLEMAN@NOTTINGHAM.AC.UK
Assistant Professor of Infection Immunology
KIN-CHOW CHANG KIN-CHOW.CHANG@NOTTINGHAM.AC.UK
Professor of Veterinary Molecular Medicine
Abstract
The struggle to control the COVID-19 pandemic is made challenging by the emergence of virulent SARS-CoV-2 variants. To gain insight into their replication dynamics, emergent Alpha (A), Beta (B) and Delta (D) SARS-CoV-2 variants were assessed for their infection performance in single variant- and co-infections. The effectiveness of thapsigargin (TG), a recently discovered broad-spectrum antiviral, against these variants was also examined. Of the 3 viruses, the D variant exhibited the highest replication rate and was most able to spread to in-contact cells; its replication rate at 24h post-infection (hpi) based on progeny viral RNA production was over 4 times that of variant A and 9 times more than the B variant. In co-infections, the D variant boosted the replication of its co-infected partners at the expense of its own initial performance. Furthermore, co-infection with AD or AB combination conferred replication synergy where total progeny (RNA) output was greater than the sum of corresponding single-variant infections. All variants were highly sensitive to TG inhibition. A single pre-infection priming dose of TG effectively blocked all single-variant infections and every combination (AB, AD, BD variants) of co-infection at greater than 95% (relative to controls) at 72hpi. Likewise, TG was effective in inhibiting each variant in active preexisting infection. In conclusion, against the current backdrop of the dominant D variant that could be further complicated by co-infection synergy with new variants, the growing list of viruses susceptible to TG, a promising host-centric antiviral, now includes a spectrum of contemporary SARS-CoV-2 viruses.
Citation
Al-Beltagi, S., Goulding, L. V., Chang, D. K., Mellits, K. H., Hayes, C. J., Gershkovich, P., …Chang, K.-C. (2021). Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin. Virulence, 12(1), 2946-2956. https://doi.org/10.1080/21505594.2021.2006960
Journal Article Type | Article |
---|---|
Acceptance Date | Nov 11, 2021 |
Online Publication Date | Dec 12, 2021 |
Publication Date | Dec 31, 2021 |
Deposit Date | Nov 18, 2021 |
Publicly Available Date | Dec 12, 2021 |
Journal | Virulence |
Print ISSN | 2150-5594 |
Electronic ISSN | 2150-5608 |
Publisher | Taylor and Francis |
Peer Reviewed | Peer Reviewed |
Volume | 12 |
Issue | 1 |
Pages | 2946-2956 |
DOI | https://doi.org/10.1080/21505594.2021.2006960 |
Keywords | Infectious Diseases; Microbiology (medical); Immunology; Microbiology; Parasitology |
Public URL | https://nottingham-repository.worktribe.com/output/6729999 |
Publisher URL | https://www.tandfonline.com/doi/full/10.1080/21505594.2021.2006960 |
Files
21505594.2021
(2.5 Mb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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