A Comprehensive Mapping of the Druggable Cavities within the SARS-CoV-2 Therapeutically Relevant Proteins by Combining Pocket and Docking Searches as Implemented in Pockets 2.0

Gervasoni, Silvia; Vistoli, Giulio; Talarico, Carmine; Manelfi, Candida; Beccari, Andrea R.; Studer, Gabriel; Tauriello, Gerardo; Waterhouse, Andrew Mark; Schwede, Torsten; Pedretti, Alessandro

doi:10.3390/ijms21145152

Submit to this Journal Review for this Journal Edit a Special Issue

Article Menu

...

Open AccessArticle

A Comprehensive Mapping of the Druggable Cavities within the SARS-CoV-2 Therapeutically Relevant Proteins by Combining Pocket and Docking Searches as Implemented in Pockets 2.0

¹,

²,

^3,4,

^3,4

Andrew Mark Waterhouse

^3,4,

Torsten Schwede

^3,4

and

Alessandro Pedretti

^1,*

Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Mangiagalli, 25, I-20133 Milano, Italy

Dompé Farmaceutici SpA, Via Campo di Pile, I-67100 L’Aquila, Italy

Biozentrum, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel, Switzerland

⁴

SIB Swiss Institute of Bioinformatics, Biozentrum, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel, Switzerland

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2020, 21(14), 5152; https://doi.org/10.3390/ijms21145152

Received: 15 June 2020 / Revised: 10 July 2020 / Accepted: 14 July 2020 / Published: 21 July 2020

(This article belongs to the Special Issue Exscalate4CoV: Innovative High Performing Computing (HPC) Strategies to Tackle Pandemic Crisis)

View Full-Text Download PDF

Browse Figures

Review Reports Citation Export

Abstract

(1) Background: Virtual screening studies on the therapeutically relevant proteins of the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) require a detailed characterization of their druggable binding sites, and, more generally, a convenient pocket mapping represents a key step for structure-based in silico studies; (2) Methods: Along with a careful literature search on SARS-CoV-2 protein targets, the study presents a novel strategy for pocket mapping based on the combination of pocket (as performed by the well-known FPocket tool) and docking searches (as performed by PLANTS or AutoDock/Vina engines); such an approach is implemented by the Pockets 2.0 plug-in for the VEGA ZZ suite of programs; (3) Results: The literature analysis allowed the identification of 16 promising binding cavities within the SARS-CoV-2 proteins and the here proposed approach was able to recognize them showing performances clearly better than those reached by the sole pocket detection; and (4) Conclusions: Even though the presented strategy should require more extended validations, this proved successful in precisely characterizing a set of SARS-CoV-2 druggable binding pockets including both orthosteric and allosteric sites, which are clearly amenable for virtual screening campaigns and drug repurposing studies. All results generated by the study and the Pockets 2.0 plug-in are available for download. View Full-Text

Keywords: SARS-CoV-2; pocket search; pocket druggability; docking simulations; virtual screening; blind docking

▼ Show Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Supplementary Material

Supplementary File 1:
PDF-Document (PDF, 414 KiB)

Share and Cite

MDPI and ACS Style

Gervasoni, S.; Vistoli, G.; Talarico, C.; Manelfi, C.; Beccari, A.R.; Studer, G.; Tauriello, G.; Waterhouse, A.M.; Schwede, T.; Pedretti, A. A Comprehensive Mapping of the Druggable Cavities within the SARS-CoV-2 Therapeutically Relevant Proteins by Combining Pocket and Docking Searches as Implemented in Pockets 2.0. Int. J. Mol. Sci. 2020, 21, 5152. https://doi.org/10.3390/ijms21145152

AMA Style

Gervasoni S, Vistoli G, Talarico C, Manelfi C, Beccari AR, Studer G, Tauriello G, Waterhouse AM, Schwede T, Pedretti A. A Comprehensive Mapping of the Druggable Cavities within the SARS-CoV-2 Therapeutically Relevant Proteins by Combining Pocket and Docking Searches as Implemented in Pockets 2.0. International Journal of Molecular Sciences. 2020; 21(14):5152. https://doi.org/10.3390/ijms21145152

Chicago/Turabian Style

Gervasoni, Silvia, Giulio Vistoli, Carmine Talarico, Candida Manelfi, Andrea R. Beccari, Gabriel Studer, Gerardo Tauriello, Andrew M. Waterhouse, Torsten Schwede, and Alessandro Pedretti. 2020. "A Comprehensive Mapping of the Druggable Cavities within the SARS-CoV-2 Therapeutically Relevant Proteins by Combining Pocket and Docking Searches as Implemented in Pockets 2.0" International Journal of Molecular Sciences 21, no. 14: 5152. https://doi.org/10.3390/ijms21145152

Find Other Styles

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Abstract views Pdf views Html views

Article Menu

A Comprehensive Mapping of the Druggable Cavities within the SARS-CoV-2 Therapeutically Relevant Proteins by Combining Pocket and Docking Searches as Implemented in Pockets 2.0

Abstract

Supplementary Material

Share and Cite

Article Metrics

Article Access Statistics

Article Access Map by Country/Region

Further Information

Guidelines

MDPI Initiatives

Follow MDPI