RT Journal Article
SR Electronic
T1 Hijacking SARS-Cov-2/ACE2 receptor interaction by natural and semi-synthetic steroidal agents acting on functional pockets on receptor binding region
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.10.144964
DO 10.1101/2020.06.10.144964
A1 Adriana Carino
A1 Federica Moraca
A1 Bianca Fiorillo
A1 Silvia Marchianò
A1 Valentina Sepe
A1 Michele Biagioli
A1 Claudia Finamore
A1 Silvia Bozza
A1 Daniela Francisci
A1 Eleonora Distrutti
A1 Bruno Catalanotti
A1 Angela Zampella
A1 Stefano Fiorucci
YR 2020
UL http://biorxiv.org/content/early/2020/06/11/2020.06.10.144964.abstract
AB The coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by the severe acute respiratory syndrome coronavirus (SARS)-CoV-2. In the light of the urgent need to identify novel approaches to be used in the emergency phase, a largely explored strategy has been the repurpose of clinically available drugs as new antivirals, by targeting different viral proteins. In this paper, we describe a drug repurposing strategy based on a virtual screening of druggable pockets located in the central β-sheet core of the SARS-CoV-2 Spike protein RBD supported by in vitro tests identifying several steroidal derivatives as SARS-CoV-2 entry inhibitors. Our results demonstrate that several potential binding sites exist in the SARS CoV-2 S protein, and that the occupancy of these pockets reduces the ability of the S protein RBD to bind to the ACE2 consensus in vitro. In particular, natural occurring and clinically available steroids as glycyrrhetinic and oleanolic acids, as well as the bile acids derivatives glyco-UDCA and obeticholic acid have been shown to be effective in preventing virus entry in the case of low viral load. All together, these results might help to define novel approaches to reduce the viral load by using SARS-CoV-2 entry inhibitors.Competing Interest StatementThis paper was supported by a research grant by BAR Pharmaceuticals S.r.L. to the Department of Pharmacy of the University of Napoli Federico II and to the Department of Surgical and Biomedical Sciences, University of Perugia. The authors declare the following competing financial interest(s): S.F., A.Z. and B.C. have filed an Italian patent application no.102020000011092 in the name of BAR Pharmaceuticals S.r.L. on the compounds described in this paper.