Hijacking SARS-CoV-2/ACE2 Receptor Interaction by Natural and Semi-synthetic Steroidal Agents Acting on Functional Pockets on the Receptor Binding Domain

Frontiers in Chemistry
A. CarinoS. Fiorucci

Abstract

The coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by the severe acute respiratory syndrome coronavirus (SARS)-CoV-2. In light of the urgent need to identify novel approaches to be used in the emergency phase, we have embarked on an exploratory campaign aimed at repurposing natural substances and clinically available drugs as potential anti-SARS-CoV2-2 agents by targeting viral proteins. Here we report on a strategy based on the virtual screening of druggable pockets located in the central β-sheet core of the SARS-CoV-2 Spike's protein receptor binding domain (RBD). By combining an in silico approach and molecular in vitro testing we have been able to identify several triterpenoid/steroidal agents that inhibit interaction of the Spike RBD with the carboxypeptidase domain of the Angiotensin Converting Enzyme (ACE2). In detail, we provide evidence that potential binding sites exist in the RBD of the SARS CoV-2 Spike protein and that occupancy of these pockets reduces the ability of the RBD to bind to the ACE2 consensus in vitro. Naturally occurring and clinically available triterpenoids such as glycyrrhetinic and oleanolic acids, as well as primary and secondary bile acids and their amidated derivativ...Continue Reading

References

Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Jun 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·M Girvan, M E J Newman
Nov 7, 2002·Biochemical and Biophysical Research Communications·Takaharu MaruyamaKenichi Tanaka
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Aug 19, 2006·Journal of Computational Chemistry·Nicholas M Glykos
Sep 11, 2007·Biochemical and Biophysical Research Communications·Hiroyuki SatoRégis Saladin
Mar 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Sandrine BelouzardGary R Whittaker
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
Jun 3, 2009·BMC Bioinformatics·Vincent Le GuillouxPierre Tuffery
May 19, 2010·Nucleic Acids Research·Peter SchmidtkePierre Tufféry
Oct 11, 2011·Journal of Cheminformatics·Noel M O'BoyleGeoffrey R Hutchison
Feb 25, 2015·Journal of Gastroenterology·Eleonora DistruttiStefano Fiorucci
Jul 2, 2015·Future Medicinal Chemistry·Valentina SepeAngela Zampella
Jul 15, 2015·Biomolecules & Therapeutics·Eun-Hye HongHeejung Yang
Nov 18, 2015·Journal of Chemical Theory and Computation·James A MaierCarlos Simmerling
Apr 15, 2016·Nature Protocols·Stefano ForliArthur J Olson
Jun 28, 2016·Nature Reviews. Microbiology·Emmie de WitVincent J Munster
Sep 1, 2016·Drug Design, Development and Therapy·Shih-Hsiang LoKung-Shing Lee
Jun 14, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michele BiagioliStefano Fiorucci
Sep 8, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Lin-Yu WangHo-Shan Niu
Aug 29, 2018·Frontiers in Immunology·Stefano FiorucciEleonora Distrutti
Sep 11, 2018·Journal of Chemical Information and Modeling·Tai-Sung LeeDarrin M York
Jul 22, 2019·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Adriana CarinoStefano Fiorucci
Jan 25, 2020·The New England Journal of Medicine·Na ZhuUNKNOWN China Novel Coronavirus Investigating and Research Team
Feb 20, 2020·The New England Journal of Medicine·Lirong ZouJie Wu
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Feb 29, 2020·The New England Journal of Medicine·Anthony S FauciRobert R Redfield
Feb 29, 2020·The New England Journal of Medicine·Wei-Jie GuanUNKNOWN China Medical Treatment Expert Group for Covid-19
Mar 5, 2020·Nature Reviews. Drug Discovery·Guangdi Li, Erik De Clercq
Mar 11, 2020·Cell·Alexandra C WallsDavid Veesler
Mar 21, 2020·Cell Discovery·Yadi ZhouFeixiong Cheng
Apr 1, 2020·Nature·Jian ShangFang Li
May 22, 2020·Gastroenterology·Cheng WangJunping Wang

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Citations

Feb 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Isabella RomeoStefano Alcaro
Feb 13, 2021·International Journal of Molecular Sciences·Niklas Grüner, Jochen Mattner
Feb 14, 2021·International Journal of Molecular Sciences·Maria Chiara di GregorioLuciano Galantini
Mar 3, 2021·Chemical Communications : Chem Comm·Marijn N MaasJasmin Mecinović
Jul 3, 2021·Biomolecules·Luisa DiomedeMario Salmona
Jul 16, 2021·Chembiochem : a European Journal of Chemical Biology·Jovan DrageljKourosh H Ebrahimi
Jun 24, 2021·Angewandte Chemie·Sridhar SreeramuluHarald Schwalbe
Aug 7, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Pasquale SibilioAntonella Verrienti
Aug 7, 2021·Computers in Biology and Medicine·Claudia Guadalupe Benítez-Cardoza, José Luis Vique-Sánchez
Aug 14, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ming-Shao TsaiChing-Yuan Wu

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Methods Mentioned

BETA
electron microscopy
Assay

Software Mentioned

Autodock
Maestro
AutoDock4
Fpocket
AutoGrid4
LigPrep
Protein Preparation Wizard
AMBER18
NetworkView
SwissModel

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