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Rucaparib blocks SARS-CoV-2 virus binding to cells and interleukin-6 release in a model of COVID-19
Henrietta Papp Ms.; Judit Bovari-Biri Ms.; Krisztina Banfai-Biri Ms.; Peter Juhasz Dr.; Mohamed Mahdi Dr.; Lilian Christina Russo Dr.; David Bajusz Dr.; Adrienn Sipos Dr.; Laszlo Petri Mr.; Agnes Kemeny Dr.; Monika Madai Dr.; Anett Kuczmog Dr.; Gyula Batta Prof.; Orsolya Mozner Ms.; Dorottya Vasko Ms.; Edit Hirsch Dr.; Peter Bohus Dr.; Gabor Mehes Prof.; Jozsef Tozser Prof.; Nicola J. Curtin Prof.; Zsuzsanna Helyes Prof.; Attila Toth Prof.; Nicolas Hoch Prof.; Ferenc Jakab Prof.; Gyorgy Keseru Prof.; Judit E. Pongracz Prof.; Peter Bai Prof..
Affiliation
  • Henrietta Papp Ms.; University of Pecs, Pecs, Hungary
  • Judit Bovari-Biri Ms.; University of Pecs, Pecs, Hungary
  • Krisztina Banfai-Biri Ms.; University of Pecs, Pecs, Hungary
  • Peter Juhasz Dr.; University of Debrecen, Debrecen, Hungary
  • Mohamed Mahdi Dr.; University of Debrecen, Debrecen, Hungary
  • Lilian Christina Russo Dr.; Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, Brazil
  • David Bajusz Dr.; Medicinal Chemistry Research Group, Research Centre for Natural Sciences, 1117, Budapest, Hungary
  • Adrienn Sipos Dr.; University of Debrecen, Debrecen, Hungary
  • Laszlo Petri Mr.; Medicinal Chemistry Research Group, Research Centre for Natural Sciences, 1117, Budapest, Hungary
  • Agnes Kemeny Dr.; University of Pecs, Pecs, Hungary
  • Monika Madai Dr.; University of Pecs, Pecs, Hungary
  • Anett Kuczmog Dr.; University of Pecs, Pecs, Hungary
  • Gyula Batta Prof.; University of Debrecen, Debrecen, Hungary
  • Orsolya Mozner Ms.; Institute of Enzymology, Research Centre for Natural Sciences, 1117, Budapest, Hungary
  • Dorottya Vasko Ms.; Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, 1111, Budapes
  • Edit Hirsch Dr.; Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, 1111, Budapes
  • Peter Bohus Dr.; Erzsebet Hospital, Satoraljaujhely, 3980, Hungary
  • Gabor Mehes Prof.; University of Debrecen, Debrecen, Hungary
  • Jozsef Tozser Prof.; University of Debrecen, Debrecen, Hungary
  • Nicola J. Curtin Prof.; Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, NE2 4HH, Newcastle upo
  • Zsuzsanna Helyes Prof.; University of Pecs, Pecs, Hungary
  • Attila Toth Prof.; University of Debrecen, Debrecen, Hungary
  • Nicolas Hoch Prof.; Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, Brazil
  • Ferenc Jakab Prof.; University of Pecs, Pecs, Hungary
  • Gyorgy Keseru Prof.; Medicinal Chemistry Research Group, Research Centre for Natural Sciences, 1117, Budapest, Hungary
  • Judit E. Pongracz Prof.; University of Pecs, Pecs, Hungary
  • Peter Bai Prof.; University of Debrecen, Debrecen, Hungary
Preprint in En | PREPRINT-MEDRXIV | ID: ppmedrxiv-22277079
ABSTRACT
Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 virus, is a major global health challenge, as there is no efficient treatment for the moderate to severe disease. ADP-ribosylation events are involved in regulating the life cycle of coronaviruses and the inflammatory reactions of the host, hence we assessed the repurposing of registered PARP inhibitors for the treatment of COVID-19. We detected high levels of oxidative stress and strong PARylation in all cell types in the lungs of COVID-19 patients. Interestingly, rucaparib, unlike other PARP inhibitors, reduced SARS-CoV-2 infection rate through binding to the conserved 493-498 amino acid region located in the spike-ACE2 interface in the spike protein and prevented viruses from binding to ACE2. In addition, the spike protein-induced overexpression of IL-6, a key cytokine in COVID-19, was inhibited by rucaparib at pharmacologically relevant concentrations. These findings build a case for repurposing rucaparib for treating COVID-19 disease.
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Full text: 1 Collection: 09-preprints Database: PREPRINT-MEDRXIV Language: En Year: 2022 Document type: Preprint
Fulltext
Add to My VHL
Print
XML
Search on Google
Full text: 1 Collection: 09-preprints Database: PREPRINT-MEDRXIV Language: En Year: 2022 Document type: Preprint