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Rucaparib blocks SARS-CoV-2 virus binding to cells and interleukin-6 release in a model of COVID-19 [article]

Henrietta Papp, Judit Bovari-Biri, Krisztina Banfai-Biri, Peter Juhasz, Mohamed Mahdi, Lilian Christina Russo, David Bajusz, Adrienn Sipos, Laszlo Petri, Agnes Kemeny, Monika Madai, Anett Kuczmog (+15 others)
2022 medRxiv   pre-print

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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
more » ... 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.
doi:10.1101/2022.06.30.22277079 fatcat:kscde6w2lrg6lplqllinvuvayy
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Henrietta Papp, Judit Bovari-Biri, Krisztina Banfai-Biri, Peter Juhasz, Mohamed Mahdi, Lilian Christina Russo, David Bajusz, Adrienn Sipos, Laszlo Petri, Agnes Kemeny, Monika Madai, Anett Kuczmog, Gyula Batta, Orsolya Mozner, Dorottya Vasko, Edit Hirsch, Peter Bohus, Gabor Mehes, Jozsef Tozser, Nicola J. Curtin, Zsuzsanna Helyes, Attila Toth, Nicolas Hoch, Ferenc Jakab, Gyorgy Keseru, Judit E. Pongracz, Peter Bai. "Rucaparib blocks SARS-CoV-2 virus binding to cells and interleukin-6 release in a model of COVID-19." medRxiv (2022)