Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin

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-...

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Autores principales:	Sarah Al-Beltagi, Leah V. Goulding, Daniel K.E. Chang, Kenneth H. Mellits, Christopher J. Hayes, Pavel Gershkovich, Christopher M. Coleman, Kin-Chow Chang
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	sars-cov-2 alpha beta delta thapsigargin antiviral emergent variants co-infection replication synergy syncytia Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/01561ffccdaa4c28ac12d389d6ccb3bf
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spelling	oai:doaj.org-article:01561ffccdaa4c28ac12d389d6ccb3bf2021-11-26T11:19:49ZEmergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin2150-55942150-560810.1080/21505594.2021.2006960https://doaj.org/article/01561ffccdaa4c28ac12d389d6ccb3bf2021-11-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2021.2006960https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608The 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 24 h 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 72 hpi. Likewise, TG was effective in inhibiting each variant in active pre-existing 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.Sarah Al-BeltagiLeah V. GouldingDaniel K.E. ChangKenneth H. MellitsChristopher J. HayesPavel GershkovichChristopher M. ColemanKin-Chow ChangTaylor & Francis Grouparticlesars-cov-2alphabetadeltathapsigarginantiviralemergent variantsco-infectionreplication synergysyncytiaInfectious and parasitic diseasesRC109-216ENVirulence, Vol 0, Iss 0 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	sars-cov-2 alpha beta delta thapsigargin antiviral emergent variants co-infection replication synergy syncytia Infectious and parasitic diseases RC109-216
spellingShingle	sars-cov-2 alpha beta delta thapsigargin antiviral emergent variants co-infection replication synergy syncytia Infectious and parasitic diseases RC109-216 Sarah Al-Beltagi Leah V. Goulding Daniel K.E. Chang Kenneth H. Mellits Christopher J. Hayes Pavel Gershkovich Christopher M. Coleman Kin-Chow Chang Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin
description	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 24 h 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 72 hpi. Likewise, TG was effective in inhibiting each variant in active pre-existing 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.
format	article
author	Sarah Al-Beltagi Leah V. Goulding Daniel K.E. Chang Kenneth H. Mellits Christopher J. Hayes Pavel Gershkovich Christopher M. Coleman Kin-Chow Chang
author_facet	Sarah Al-Beltagi Leah V. Goulding Daniel K.E. Chang Kenneth H. Mellits Christopher J. Hayes Pavel Gershkovich Christopher M. Coleman Kin-Chow Chang
author_sort	Sarah Al-Beltagi
title	Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin
title_short	Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin
title_full	Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin
title_fullStr	Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin
title_full_unstemmed	Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin
title_sort	emergent sars-cov-2 variants: comparative replication dynamics and high sensitivity to thapsigargin
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/01561ffccdaa4c28ac12d389d6ccb3bf
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Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin

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