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Open AccessArticle

Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus

1
School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Nottingham LE12 5RD, UK
2
The Pirbright Institute, Ash Road, Pirbright, Woking GU24 0NF, UK
3
Animal and Plant Health Agency (APHA), Weybridge, Woodham Lane, Addlestone KT15 3NB, UK
4
Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China
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School of Biosciences, University of Nottingham, Sutton Bonington, Nottingham LE12 5RD, UK
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School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK
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School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK
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School of Medicine, University of Nottingham, University Park, Nottingham NG7 2RD, UK
*
Author to whom correspondence should be addressed.
These authors contribute equally to this work.
Academic Editor: Vittorio Sambri
Viruses 2021, 13(2), 234; https://doi.org/10.3390/v13020234
Received: 14 January 2021 / Revised: 23 January 2021 / Accepted: 26 January 2021 / Published: 3 February 2021
(This article belongs to the Special Issue State-of-the-Art Emerging Respiratory Viruses in Europe)
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) Ca2+ 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. View Full-Text
Keywords: thapsigargin; inhibitor; antiviral; SARS-CoV-2; coronavirus OC43; respiratory syncytial virus; influenza virus; broad-spectrum; innate immunity; mouse; remdesivir; ribavirin; oseltamivir thapsigargin; inhibitor; antiviral; SARS-CoV-2; coronavirus OC43; respiratory syncytial virus; influenza virus; broad-spectrum; innate immunity; mouse; remdesivir; ribavirin; oseltamivir
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MDPI and ACS Style

Al-Beltagi, S.; Preda, C.A.; Goulding, L.V.; James, J.; Pu, J.; Skinner, P.; Jiang, Z.; Wang, B.L.; Yang, J.; Banyard, A.C.; Mellits, K.H.; Gershkovich, P.; Hayes, C.J.; Nguyen-Van-Tam, J.; Brown, I.H.; Liu, J.; Chang, K.-C. Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus. Viruses 2021, 13, 234. https://doi.org/10.3390/v13020234

AMA Style

Al-Beltagi S, Preda CA, Goulding LV, James J, Pu J, Skinner P, Jiang Z, Wang BL, Yang J, Banyard AC, Mellits KH, Gershkovich P, Hayes CJ, Nguyen-Van-Tam J, Brown IH, Liu J, Chang K-C. Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus. Viruses. 2021; 13(2):234. https://doi.org/10.3390/v13020234

Chicago/Turabian Style

Al-Beltagi, Sarah; Preda, Cristian A.; Goulding, Leah V.; James, Joe; Pu, Juan; Skinner, Paul; Jiang, Zhimin; Wang, Belinda L.; Yang, Jiayun; Banyard, Ashley C.; Mellits, Kenneth H.; Gershkovich, Pavel; Hayes, Christopher J.; Nguyen-Van-Tam, Jonathan; Brown, Ian H.; Liu, Jinhua; Chang, Kin-Chow. 2021. "Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus" Viruses 13, no. 2: 234. https://doi.org/10.3390/v13020234

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