PMID- 33546185
OWN - NLM
STAT- MEDLINE
DCOM- 20210217
LR  - 20231110
IS  - 1999-4915 (Electronic)
IS  - 1999-4915 (Linking)
VI  - 13
IP  - 2
DP  - 2021 Feb 3
TI  - Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: 
      Coronavirus, Respiratory Syncytial Virus and Influenza A Virus.
LID - 10.3390/v13020234 [doi]
LID - 234
AB  - The long-term control strategy of SARS-CoV-2 and other major respiratory viruses 
      needs to include antivirals to treat acute infections, in addition to the 
      judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled 
      out for mass vaccination, the modest number of antivirals in use or development 
      for any disease bears testament to the challenges of antiviral development. We 
      recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of 
      the sarcoplasmic/endoplasmic reticulum (ER) Ca(2+) ATPase pump, induces a potent 
      host innate immune antiviral response that blocks influenza A virus replication. 
      Here we show that TG is also highly effective in blocking the replication of 
      respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and 
      influenza A virus in immortalized or primary human cells. TG's antiviral 
      performance was significantly better than remdesivir and ribavirin in their 
      respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to 
      coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 
      H1N1) in separate infections as in co-infections. Post-infection oral gavage of 
      acid-stable TG protected mice against a lethal influenza virus challenge. 
      Together with its ability to inhibit the different viruses before or during 
      active infection, and with an antiviral duration of at least 48 h post-TG 
      exposure, we propose that TG (or its derivatives) is a promising broad-spectrum 
      inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.
FAU - Al-Beltagi, Sarah
AU  - Al-Beltagi S
AUID- ORCID: 0000-0002-4034-2174
AD  - School of Veterinary Medicine and Science, University of Nottingham, Sutton 
      Bonington, Nottingham LE12 5RD, UK.
FAU - Preda, Cristian Alexandru
AU  - Preda CA
AUID- ORCID: 0000-0002-5906-8769
AD  - School of Veterinary Medicine and Science, University of Nottingham, Sutton 
      Bonington, Nottingham LE12 5RD, UK.
FAU - Goulding, Leah V
AU  - Goulding LV
AUID- ORCID: 0000-0002-6371-8840
AD  - The Pirbright Institute, Ash Road, Pirbright, Woking GU24 0NF, UK.
FAU - James, Joe
AU  - James J
AUID- ORCID: 0000-0002-9673-3684
AD  - Animal and Plant Health Agency (APHA), Weybridge, Woodham Lane, Addlestone KT15 
      3NB, UK.
FAU - Pu, Juan
AU  - Pu J
AD  - Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of 
      Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, 
      Beijing 100193, China.
FAU - Skinner, Paul
AU  - Skinner P
AUID- ORCID: 0000-0001-5505-3343
AD  - Animal and Plant Health Agency (APHA), Weybridge, Woodham Lane, Addlestone KT15 
      3NB, UK.
FAU - Jiang, Zhimin
AU  - Jiang Z
AUID- ORCID: 0000-0002-9797-6493
AD  - Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of 
      Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, 
      Beijing 100193, China.
FAU - Wang, Belinda Lei
AU  - Wang BL
AD  - School of Veterinary Medicine and Science, University of Nottingham, Sutton 
      Bonington, Nottingham LE12 5RD, UK.
FAU - Yang, Jiayun
AU  - Yang J
AD  - School of Veterinary Medicine and Science, University of Nottingham, Sutton 
      Bonington, Nottingham LE12 5RD, UK.
FAU - Banyard, Ashley C
AU  - Banyard AC
AUID- ORCID: 0000-0002-1286-9825
AD  - Animal and Plant Health Agency (APHA), Weybridge, Woodham Lane, Addlestone KT15 
      3NB, UK.
FAU - Mellits, Kenneth H
AU  - Mellits KH
AD  - School of Biosciences, University of Nottingham, Sutton Bonington, Nottingham 
      LE12 5RD, UK.
FAU - Gershkovich, Pavel
AU  - Gershkovich P
AD  - School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 
      2RD, UK.
FAU - Hayes, Christopher J
AU  - Hayes CJ
AUID- ORCID: 0000-0003-1692-3646
AD  - School of Chemistry, University of Nottingham, University Park, Nottingham NG7 
      2RD, UK.
FAU - Nguyen-Van-Tam, Jonathan
AU  - Nguyen-Van-Tam J
AD  - School of Medicine, University of Nottingham, University Park, Nottingham NG7 
      2RD, UK.
FAU - Brown, Ian H
AU  - Brown IH
AD  - Animal and Plant Health Agency (APHA), Weybridge, Woodham Lane, Addlestone KT15 
      3NB, UK.
FAU - Liu, Jinhua
AU  - Liu J
AD  - Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of 
      Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, 
      Beijing 100193, China.
FAU - Chang, Kin-Chow
AU  - Chang KC
AUID- ORCID: 0000-0002-6602-7447
AD  - School of Veterinary Medicine and Science, University of Nottingham, Sutton 
      Bonington, Nottingham LE12 5RD, UK.
LA  - eng
GR  - MC_PC_18058/MRC_/Medical Research Council/United Kingdom
GR  - BB/M008770/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210203
PL  - Switzerland
TA  - Viruses
JT  - Viruses
JID - 101509722
RN  - 0 (Antiviral Agents)
RN  - 49717AWG6K (Ribavirin)
RN  - 67526-95-8 (Thapsigargin)
SB  - IM
MH  - Animals
MH  - Antiviral Agents/*pharmacology/therapeutic use
MH  - Betacoronavirus/*drug effects/physiology
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Coronavirus OC43, Human/*drug effects/physiology
MH  - Endoplasmic Reticulum Stress
MH  - Humans
MH  - Influenza A Virus, H1N1 Subtype/*drug effects/physiology
MH  - Mice
MH  - Microbial Sensitivity Tests
MH  - Orthomyxoviridae Infections/drug therapy/virology
MH  - Respiratory Syncytial Virus, Human/*drug effects/physiology
MH  - Ribavirin/pharmacology
MH  - SARS-CoV-2/*drug effects/physiology
MH  - Thapsigargin/*pharmacology/therapeutic use
MH  - Virus Replication/drug effects
PMC - PMC7913267
OTO - NOTNLM
OT  - SARS-CoV-2
OT  - antiviral
OT  - broad-spectrum
OT  - coronavirus OC43
OT  - influenza virus
OT  - inhibitor
OT  - innate immunity
OT  - mouse
OT  - oseltamivir
OT  - remdesivir
OT  - respiratory syncytial virus
OT  - ribavirin
OT  - thapsigargin
COIS- J.N.-V.-T. is currently seconded to the Department of Health and Social Care, 
      England (DHSC). The views expressed in this manuscript are those of the authors 
      and not necessarily those of DHSC. The remaining authors declare no conflict of 
      interest.
EDAT- 2021/02/07 06:00
MHDA- 2021/02/18 06:00
PMCR- 2021/02/03
CRDT- 2021/02/06 01:02
PHST- 2021/01/14 00:00 [received]
PHST- 2021/01/23 00:00 [revised]
PHST- 2021/01/26 00:00 [accepted]
PHST- 2021/02/06 01:02 [entrez]
PHST- 2021/02/07 06:00 [pubmed]
PHST- 2021/02/18 06:00 [medline]
PHST- 2021/02/03 00:00 [pmc-release]
AID - v13020234 [pii]
AID - viruses-13-00234 [pii]
AID - 10.3390/v13020234 [doi]
PST - epublish
SO  - Viruses. 2021 Feb 3;13(2):234. doi: 10.3390/v13020234.