PMID- 34793280
OWN - NLM
STAT- MEDLINE
DCOM- 20211220
LR  - 20231108
IS  - 2150-5608 (Electronic)
IS  - 2150-5594 (Print)
IS  - 2150-5594 (Linking)
VI  - 12
IP  - 1
DP  - 2021 Dec
TI  - Emergent SARS-CoV-2 variants: comparative replication dynamics and high 
      sensitivity to thapsigargin.
PG  - 2946-2956
LID - 10.1080/21505594.2021.2006960 [doi]
AB  - 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 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.
FAU - Al-Beltagi, Sarah
AU  - Al-Beltagi S
AUID- ORCID: 0000-0002-4034-2174
AD  - School of Veterinary Medicine and Science, University of Nottingham, Nottingham, 
      UK.
FAU - Goulding, Leah V
AU  - Goulding LV
AUID- ORCID: 0000-0002-6371-8840
AD  - The Pirbright Institute, Woking, UK.
FAU - Chang, Daniel K E
AU  - Chang DKE
AUID- ORCID: 0000-0003-1201-6360
AD  - Department of Chemical and Biological Engineering, University of Sheffield, 
      Sheffield, UK.
FAU - Mellits, Kenneth H
AU  - Mellits KH
AUID- ORCID: 0000-0003-1803-9184
AD  - School of Biosciences, University of Nottingham, Nottingham, UK.
FAU - Hayes, Christopher J
AU  - Hayes CJ
AUID- ORCID: 0000-0003-1692-3646
AD  - School of Chemistry, University of Nottingham, University Park, Nottingham, UK.
FAU - Gershkovich, Pavel
AU  - Gershkovich P
AUID- ORCID: 0000-0003-3136-0933
AD  - School of Pharmacy, University of Nottingham, University Park, Nottingham, UK.
FAU - Coleman, Christopher M
AU  - Coleman CM
AUID- ORCID: 0000-0002-7306-8407
AD  - School of Life Sciences, University of Nottingham, University Park, Nottingham, 
      UK.
FAU - Chang, Kin-Chow
AU  - Chang KC
AUID- ORCID: 0000-0002-6602-7447
AD  - School of Veterinary Medicine and Science, University of Nottingham, Nottingham, 
      UK.
LA  - eng
GR  - MC_PC_18058/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Virulence
JT  - Virulence
JID - 101531386
RN  - 0 (Antiviral Agents)
RN  - 67526-95-8 (Thapsigargin)
RN  - SARS-CoV-2 variants
SB  - IM
MH  - Antiviral Agents/pharmacology/therapeutic use
MH  - *Coinfection
MH  - Humans
MH  - Pandemics
MH  - *SARS-CoV-2/drug effects
MH  - *Thapsigargin/pharmacology/therapeutic use
MH  - *COVID-19 Drug Treatment
PMC - PMC8667886
OTO - NOTNLM
OT  - Alpha
OT  - Beta
OT  - Delta
OT  - SARS-CoV-2
OT  - antiviral
OT  - co-infection
OT  - emergent variants
OT  - replication synergy
OT  - syncytia
OT  - thapsigargin
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2021/11/19 06:00
MHDA- 2021/12/21 06:00
PMCR- 2021/12/12
CRDT- 2021/11/18 17:15
PHST- 2021/11/19 06:00 [pubmed]
PHST- 2021/12/21 06:00 [medline]
PHST- 2021/11/18 17:15 [entrez]
PHST- 2021/12/12 00:00 [pmc-release]
AID - 2006960 [pii]
AID - 10.1080/21505594.2021.2006960 [doi]
PST - ppublish
SO  - Virulence. 2021 Dec;12(1):2946-2956. doi: 10.1080/21505594.2021.2006960.