A multi-targeting approach to fight COVID-19
Contact person: EmiliaMaria Pedone, emilia.pedone
cnr.it
Actors: Laura Zaccaro, lzaccarounina.it, Annarita Del Gatto, annarita.delgattocnr.it, EmiliaMaria Pedone, emilia.pedonecnr.it, Luciano Pirone, luciano.pironecnr.it, Sonia Di Gaetano, digaetanunina.it,
Research areas: Macromolecules for biomedical and biotechnological applications, Structure and function of proteins involved in physio-pathologic processes, Small molecules and peptides/modified peptides for diagnostic, therapeutic and biotechnological applications,
Keywords: Sars Cov 2, Galectin, Integrin, Ace2, Spike Protein, Ganglioside, Repurposing Drugs, Inhibitors
Contact person: EmiliaMaria Pedone, emilia.pedone
cnr.itActors: Laura Zaccaro, lzaccaro
unina.it, Annarita Del Gatto, annarita.delgattocnr.it, EmiliaMaria Pedone, emilia.pedonecnr.it, Luciano Pirone, luciano.pironecnr.it, Sonia Di Gaetano, digaetanunina.it, Description:
The public health has declared an international state of emergency due to the spread of a new coronavirus (SARS-CoV-2) representing a real pandemic threat so that to find potential therapeutic agents is a dire need. Since any traditional drug discovery program is a time-consuming and costly process requiring decades to be completed, in silico repurposing of existing drugs should be the preferred way for rapidly selecting compounds.
The public health has declared an international state of emergency due to the spread of a new coronavirus (SARS-CoV-2) representing a real pandemic threat so that to find potential therapeutic agents is a dire need. Since any traditional drug discovery program is a time-consuming and costly process requiring decades to be completed, in silico repurposing of existing drugs should be the preferred way for rapidly selecting compounds.
The aim of this recent research line is to develop a combined experimental-computational platform for repurposing drugs against different protein targets involved in SARS-CoV-2 infection.
In this context, we focused not only on some already characterized targets for SARS-CoV-2 i.e. the main protease (MPro) and the papain-like protease, but also on two further emerging targets in the Spike protein sequence besides ACE2 interaction site: a new type of ganglioside-binding domain (GBD), which seems to reside exactly in the galectin-like domain and a RGD sequence, generated by evolutionary mutation, recognized by the membrane receptor integrins.
Moreover, our idea is that ligands modulating the interaction with integrins or, at the same level, with a sugar through the galectin-domain, could represent a suitable therapeutic application.
These indications open a new scenario for the future COVID-19 treatment where a multi-targeting therapy could be applied considering ACE2, integrin and galectin domain inhibitors. To this aim bioinformatics, biochemical, biophysical and cellular methodologies will be used.
Figures:
Selected papers:
Pirone L, Del Gatto A, Di Gaetano S, Saviano M, Capasso D, Zaccaro L, Pedone A Multi-Targeting Approach to Fight SARS-CoV-2 Attachment.E.Front Mol Biosci. 2020 Aug 3;7:186. doi: 10.3389/fmolb.2020.00186. eCollection 2020.
Fantini et al. Leveraging coronavirus binding to gangliosides for innovative vaccine and therapeutic strategies against COVID-19 B.B.R.C in press 2020
Delre P, Caporuscio F, Saviano M, Mangiatordi GF Repurposing Known Drugs as Covalent and Non-covalent Inhibitors of the SARS-CoV-2 Papain-Like Protease Front. Chem., 16 November 2020 | doi.org/10.3389/fchem.2020.594009
Pirone L, Del Gatto A, Di Gaetano S, Saviano M, Capasso D, Zaccaro L, Pedone A Multi-Targeting Approach to Fight SARS-CoV-2 Attachment.E.Front Mol Biosci. 2020 Aug 3;7:186. doi: 10.3389/fmolb.2020.00186. eCollection 2020.
Fantini et al. Leveraging coronavirus binding to gangliosides for innovative vaccine and therapeutic strategies against COVID-19 B.B.R.C in press 2020
Delre P, Caporuscio F, Saviano M, Mangiatordi GF Repurposing Known Drugs as Covalent and Non-covalent Inhibitors of the SARS-CoV-2 Papain-Like Protease Front. Chem., 16 November 2020 | doi.org/10.3389/fchem.2020.594009
A multi-targeting approach to fight COVID-19
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