Coronavirus Library


Small molecule screening compounds for coronavirus / SARS-CoV-2 / COVID-19 drug discovery

Highlights

  • Generated in collaboration with a leading academic group
  • High quality, PAINS-free, lead-like and drug-like small molecule compounds
  • For SARS-CoV-2 / COVID-19 and other coronavirus research
  • More than 15,000 compounds available covering 17 targets
  • Purchase the full library or custom select a subset

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously known as 2019 novel coronavirus (2019-nCoV), has spread rapidly across the globe, creating an unparalleled global health burden and spurring a deepening economic crisis. As of June 2020, more than 6 months into the outbreak, there were no approved vaccines or small-molecule drugs available which were specifically developed for COVID-19. Developing drugs that target multiple points in the viral life cycle could serve as a strategy to tackle the current as well as future coronavirus pandemics.

In August 2020, ChemBridge released the new Coronavirus Library, which offers more than 15,000 compounds with potential to interact with SARS-CoV-2 viral targets or the host target ACE2. Compounds in the Coronavirus Library were selected in collaboration with the Wagner Lab at Harvard using the Virtual Flow methodology developed and published by the Wagner Lab. Details on the Virtual Flow methodology are published in Gorgulla, C., Boeszoermenyi, A., Wang, Z. et al. "An open-source drug discovery platform enables ultra-large virtual screens" Nature 580, 663–668 (2020). This SARS-CoV-2 / COVID-19 small molecule library may also have application in other coronavirus research programs.


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to download a copy of the Coronavirus Library product sheet.


Methodology

ChemBridge’s stock of more than 1.3 million compounds were prepared and docked against each of 40 different target sites on 17 different potential viral and host targets using the Virtual Flow screening platform. Top ranked compounds were further filtered to ensure that the Coronavirus Library included only high quality, lead-like or drug-like compounds free of undesirable chemical functionalities and free of PAINS structural alerts. The compound count per target ranges from 1,000 to 5,000 with 1,000 to 2,000 compounds per site screened.

Structures from ChemBridge stock were prepared with VirtualFlow for Ligand Preparation (VFLP)1. For each virtual screen a single target structure was used, and the protein was held rigid. QuickVina-W2 was used to perform a blind docking procedure for the HR1 domain of the spike protein, the RNA binding interface of the nucleoprotein, the RNA binding site of nsp12, as well as for nsp7 and ORF7a. For all the other site specific docking routines, QuickVina 23 was used. Both docking programs are based on AutoDock Vina4. The receptor structures were prepared with AutoDockTools5 from the PDB format to the PDBQT format.


Targets

Protein Alternate Name(s) Site(s) Docked
SpikeS-proteinSpike RBD-ACE2 interface, HR1 domain
TMPRSS2Transmembrane protease serine 2Active site
ORF7aProtein 7aBlind docking
Phosphatase(macro) X domainClosed active site, open active site
PLproPapain-like proteaseActive site, accessory pocket, DUB binding site
MproMain protease Active site, dimerization site, alpha-helix 5 attachment site
nsp7Replicase polyprotein 1abBlind docking of nsp8 and nsp12 binding interfaces
nsp8Primase complexnsp7 binding interface, nsp12 binding interface
nsp9ReplicaseDimerization interface
nsp10N/Ansp14 binding interface, nsp16 binding interface
nsp12RNA dependent RNA-polymeraseRNA binding interface, nucleotide binding site, nsp8 binding interface, nsp7 binding interface
nsp13HelicaseRNA binding interface, active site
nsp14Exoribonuclease or N7 methyltransferasensp10 binding interface, ExoN active site, N7-MT active site
nsp15EndoribonucleaseActive site
nsp162’-O methyltransferase2’-O MT active site, nsp10 binding interface
NucleoproteinRibonucleocapsid proteinNTD RNA binding site, NTD oligomerization site, CTD dimerization interface, CTD oligomerization site
ACE2Angiotensin-converting enzyme 2Spike RBD binding region, dynamic pocket 1 near spike RBD, dynamic pocket 2 near spike RBD

Format

  • Custom select from more than 15,000 Coronavirus Library compounds or purchase all available compounds.
  • The "Target" field in the structure file indicates the potential protein target(s).
  • Available in 96-well or 384-well format including acoustic compatible plates
  • Minimum order amount of 1 micromole with amounts as low as 0.25 micromole available for orders of 2,000 or more compounds
  • Compounds are available dry or as DMSO solutions

For more information or a file of compound structures, please email ChemBridge Sales.

References

  1. Gorgulla, C., Boeszoermenyi, A., Wang, Z. et al. An open-source drug discovery platform enables ultra-large virtual screens. Nature 580, 663–668 (2020).
  2. Protein-Ligand Blind Docking Using QuickVina-W With Inter-Process Spatio-Temporal Integration. Nafisa M. Hassan, Amr A. Alhossary, Yuguang Mu and Chee-Keong Kwoh. Nature Scientific Reports 7(1) (2017). DOI:10.1038/s41598-017-15571-7
  3. Fast, Accurate, and Reliable Molecular Docking with QuickVina 2. Amr Alhossary, Stephanus Daniel Handoko, Yuguang Mu, and Chee-Keong Kwoh. Bioinformatics (2015) 31 (13): 2214-2216. DOI:10.1093/bioinformatics/btv082
  4. O. Trott, A. J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading, Journal of Computational Chemistry 31 (2010) 455-461.
  5. Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S. and Olson, A. J. (2009) Autodock4 and AutoDockTools4: automated docking with selective receptor flexiblity. J. Computational Chemistry 2009, 16: 2785-91.

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