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Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus.
Al-Beltagi, Sarah; Preda, Cristian Alexandru; Goulding, Leah V; James, Joe; Pu, Juan; Skinner, Paul; Jiang, Zhimin; Wang, Belinda Lei; 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.
  • Al-Beltagi S; School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Nottingham LE12 5RD, UK.
  • Preda CA; School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Nottingham LE12 5RD, UK.
  • Goulding LV; The Pirbright Institute, Ash Road, Pirbright, Woking GU24 0NF, UK.
  • James J; Animal and Plant Health Agency (APHA), Weybridge, Woodham Lane, Addlestone KT15 3NB, UK.
  • Pu J; Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China.
  • Skinner P; Animal and Plant Health Agency (APHA), Weybridge, Woodham Lane, Addlestone KT15 3NB, UK.
  • Jiang Z; Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China.
  • Wang BL; School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Nottingham LE12 5RD, UK.
  • Yang J; School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Nottingham LE12 5RD, UK.
  • Banyard AC; Animal and Plant Health Agency (APHA), Weybridge, Woodham Lane, Addlestone KT15 3NB, UK.
  • Mellits KH; School of Biosciences, University of Nottingham, Sutton Bonington, Nottingham LE12 5RD, UK.
  • Gershkovich P; School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
  • Hayes CJ; School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
  • Nguyen-Van-Tam J; School of Medicine, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
  • Brown IH; Animal and Plant Health Agency (APHA), Weybridge, Woodham Lane, Addlestone KT15 3NB, UK.
  • Liu J; Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China.
  • Chang KC; School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Nottingham LE12 5RD, UK.
Viruses ; 13(2)2021 02 03.
Artículo en Inglés | MEDLINE | ID: covidwho-1060766
ABSTRACT
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.
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Texto completo: Disponible Colección: Bases de datos internacionales Base de datos: MEDLINE Asunto principal: Antivirales / Virus Sincitial Respiratorio Humano / Tapsigargina / Coronavirus Humano OC43 / Subtipo H1N1 del Virus de la Influenza A / Betacoronavirus / SARS-CoV-2 Tópicos: Vacunas Límite: Animales / Humanos Idioma: Inglés Año: 2021 Tipo del documento: Artículo País de afiliación: V13020234

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Texto completo: Disponible Colección: Bases de datos internacionales Base de datos: MEDLINE Asunto principal: Antivirales / Virus Sincitial Respiratorio Humano / Tapsigargina / Coronavirus Humano OC43 / Subtipo H1N1 del Virus de la Influenza A / Betacoronavirus / SARS-CoV-2 Tópicos: Vacunas Límite: Animales / Humanos Idioma: Inglés Año: 2021 Tipo del documento: Artículo País de afiliación: V13020234