Skip to main content

ChEMBL_27 SARS-CoV-2 release



The COVID-19 pandemic has resulted in an unprecedented effort across the global scientific community. Drug discovery groups are contributing in several ways, including the screening of compounds to identify those with potential anti-SARS-CoV-2 activity. When the compounds being assayed are marketed drugs or compounds in clinical development then this may identify potential repurposing opportunities (though there are many other factors to consider including safety and PK/PD considerations; see for example https://www.medrxiv.org/content/10.1101/2020.04.16.20068379v1.full.pdf+html). The results from such compound screening can also help inform and drive our understanding of the complex interplay between virus and host at different stages of infection.

Several large-scale drug screening studies have now been described and made available as pre-prints or as peer-reviewed publications. The ChEMBL team has been following these developments with significant interest, and as a contribution to the overall COVID-19 effort we have curated the bioactivity data reported in these studies. Many of the compounds used in these studies have significant data and information already available in ChEMBL; one of our goals is to enable users to view the COVID-19 results alongside existing data and to be able to compare results from different labs (e.g. for the same compounds). We have chosen for this special release to focus on those studies which use cell-based assays to screen such well-established compounds for anti-viral activity.

Drug names were extracted from each publication and mapped to ChEMBL compound identifiers and/or chemical structures, using a combination of automated mapping and manual curation. These were incorporated into the database, along with the relevant assay/activity information, to produce the new release of ChEMBL. Full details can be found in the release notes; these datasets been incorporated as a new source (src_id = 52, SARS-CoV-2 Screening Data) and can be accessed via this link.

Here is a summary of the 8 data sets that we have curated:

CHEMBL4303084:
Jeon et al. (2020) Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs. Preprint DOI: 10.1101/2020.03.20.999730
In this study, 48 approved drugs were tested against SARS-CoV-2 in a Vero cell assay.

CHEMBL4303773:
Gordon et al. (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Publication DOI: 10.1038/s41586-020-2286-9, PMID: 32353859
Following identification of host-viral protein interactions, a set of 75 compounds believed to be active against these proteins were tested in Vero E6 cells for activity against SARS-CoV-2.

CHEMBL4303082:
Riva et al. (2020) A Large-scale Drug Repositioning Survey for SARS-CoV-2 Antivirals. Preprint DOI: 10.1101/2020.04.16.044016
The ReFRAME drug repurposing library of 12K compounds was tested for activity against SARS-CoV-2 in Vero E6 cells. 18 active compounds were reported.

CHEMBL4303097:
Touret et al. (2020) In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication. Preprint DOI: 10.1101/2020.04.03.023846
The Prestwick Chemical Library of 1520 approved drugs was screened to identify compounds active against SARS-CoV-2 in a Vero E6 cell assay.

CHEMBL4303087:
Weston et al. (2020) Broad anti-coronaviral activity of FDA approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo. Preprint DOI: 10.1101/2020.03.25.008482
20 approved drugs that had previously shown activity against SARS-CoV and MERS-CoV were tested for activity against SARS-CoV-2 in a Vero E6 cell assay. A number of compounds were subsequently tested for their effect on viral fusion, and two compounds (chloroquine and chlorpromazine) were tested in a SARS-CoV infected mouse model.

CHEMBL4303101:
Ellinger et al. (2020) Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection. Preprint DOI: 10.21203/rs.3.rs-23951/v1
A large drug/candidate library (5632 compounds) was screened for activity against SARS-CoV-2 in human Caco-2 cells using an imaging assay. IC50 values were calculated for 67 compounds.

CHEMBL4303122:
Heiser et al. (2020) Identification of potential treatments for COVID-19 through artificial intelligence-enabled phenomic analysis of human cells infected with SARS-CoV-2. Preprint DOI: 10.1101/2020.04.21.054387
1670 approved drugs and reference compounds were screened for activity against SARS-CoV-2 in human renal cortical epithelial (HRCE) cells using an AI image-analysis algorithm.

CHEMBL4303121:
Si et al. (2020) Human organs-on-chips as tools for repurposing approved drugs as potential influenza and COVID19 therapeutics in viral pandemics. Preprint DOI: 10.1101/2020.04.13.039917
Effect on SARS-CoV-2 viral entry in Huh-7 cells was assessed for 7 approved drugs that have previously shown activity against other viral infections. The compounds were then assessed for antiviral activity in human lung Airway Chip at their reported Cmax. Note, this study also included influenza data, which is not currently included in this ChEMBL release.

So which drugs demonstrate activity in these assays?

There are 133 compounds with a reported IC50/EC50 better than 10uM in one or more studies and 41 compounds with an IC50/EC50 better than 1uM in one or more studies (but please bear in mind that not all studies/assays reported IC50/EC50 measurements). It is important to note that most of the studies included here also assessed the cytotoxicity of the drugs in the absence of viral infection. Some showed significant cytotoxicity in addition to their antiviral activity, at the concentrations tested, so this information should be taken into account when analysing the data. For example, of the 133 compounds with activity < 10uM, only 72 of these have a reported 'Selectivity index' > 3 (ratio of cell cytotoxicity/antiviral activity) and 44 of these are approved drugs. By switching to the Heatmap view for these compounds in ChEMBL, you can also see what other reported activities these compounds have:



The overlap in terms of which compounds are active between the different studies is fairly low. Only a handful of compounds are active in more than one study. When considering all of the different activity types measured, 14 compounds could be considered active/weakly active in more than one study and only 5 compounds were active in three or more studies: remdesivir (Ellinger, Heiser, Riva, Touret), chloroquine (Heiser, Si, Jeon), hydroxychloroquine (Gordon, Touret, Weston), mefloquine (Jeon, Ellinger, Weston) and amodiaquine (Jeon, Si, Weston).

There may be many reasons for the variation in these results, particularly as these can be very complex assays to set up and run. Assays may also differ in the cell type used (Vero-derived cell lines from African Green Monkey vs human cell lines/tissue), the SARS-CoV-2 isolates used, multiplicity of infection (MOI) tested, and the assay type/detection method.

We will continue to monitor closely COVID-19 progress as more studies are disclosed. We are very happy to receive feedback on this release of ChEMBL via chembl-help@ebi.ac.uk.

Finally, we would like to acknowledge the tremendous efforts of the researchers who have established the assays and generated the data so speedily.

Comments

Popular posts from this blog

Improvements in SureChEMBL's chemistry search and adoption of RDKit

    Dear SureChEMBL users, If you frequently rely on our "chemistry search" feature, today brings great news! We’ve recently implemented a major update that makes your search experience faster than ever. What's New? Last week, we upgraded our structure search engine by aligning it with the core code base used in ChEMBL . This update allows SureChEMBL to leverage our FPSim2 Python package , returning results in approximately one second. The similarity search relies on 256-bit RDKit -calculated ECFP4 fingerprints, and a single instance requires approximately 1 GB of RAM to run. SureChEMBL’s FPSim2 file is not currently available for download, but we are considering generating it periodicaly and have created it once for you to try in Google Colab ! For substructure searches, we now also use an RDKit -based solution via SubstructLibrary , which returns results several times faster than our previous implementation. Additionally, structure search results are now sorted by

ChEMBL brings drug bioactivity data to the Protein Data Bank in Europe

In the quest to develop new drugs, understanding the 3D structure of molecules is crucial. Resources like the Protein Data Bank in Europe (PDBe) and the Cambridge Structural Database (CSD) provide these 3D blueprints for many biological molecules. However, researchers also need to know how these molecules interact with their biological target – their bioactivity. ChEMBL is a treasure trove of bioactivity data for countless drug-like molecules. It tells us how strongly a molecule binds to a target, how it affects a biological process, and even how it might be metabolized. But here's the catch: while ChEMBL provides extensive information on a molecule's activity and cross references to other data sources, it doesn't always tell us if a 3D structure is available for a specific drug-target complex. This can be a roadblock for researchers who need that structural information to design effective drugs. Therefore, connecting ChEMBL data with resources like PDBe and CSD is essen

New SureChEMBL announcement

(Generated with DALL-E 3 ∙ 30 October 2023 at 1:48 pm) We have some very exciting news to report: the new SureChEMBL is now available! Hooray! What is SureChEMBL, you may ask. Good question! In our portfolio of chemical biology services, alongside our established database of bioactivity data for drug-like molecules ChEMBL , our dictionary of annotated small molecule entities ChEBI , and our compound cross-referencing system UniChem , we also deliver a database of annotated patents! Almost 10 years ago , EMBL-EBI acquired the SureChem system of chemically annotated patents and made this freely accessible in the public domain as SureChEMBL. Since then, our team has continued to maintain and deliver SureChEMBL. However, this has become increasingly challenging due to the complexities of the underlying codebase. We were awarded a Wellcome Trust grant in 2021 to completely overhaul SureChEMBL, with a new UI, backend infrastructure, and new f

Improved querying for SureChEMBL

    Dear SureChEMBL users, Earlier this year we ran a survey to identify what you, the users, would like to see next in SureChEMBL. Thank you for offering your feedback! This gave us the opportunity to have some interesting discussions both internally and externally. While we can't publicly reveal precisely our plans for the coming months (everything will be delivered at the right time), we can at least say that improving the compound structure extraction quality is a priority. Unfortunately, the change won't happen overnight as reprocessing 167 millions patents takes a while. However, the good news is that the new generation of optical chemical structure recognition shows good performance, even for patent images! We hope we can share our results with you soon. So in the meantime, what are we doing? You may have noticed a few changes on the SureChEMBL main page. No more "Beta" flag since we consider the system to be stable enough (it does not mean that you will never

ChEMBL 34 is out!

We are delighted to announce the release of ChEMBL 34, which includes a full update to drug and clinical candidate drug data. This version of the database, prepared on 28/03/2024 contains:         2,431,025 compounds (of which 2,409,270 have mol files)         3,106,257 compound records (non-unique compounds)         20,772,701 activities         1,644,390 assays         15,598 targets         89,892 documents Data can be downloaded from the ChEMBL FTP site:  https://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/releases/chembl_34/ Please see ChEMBL_34 release notes for full details of all changes in this release:  https://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/releases/chembl_34/chembl_34_release_notes.txt New Data Sources European Medicines Agency (src_id = 66): European Medicines Agency's data correspond to EMA drugs prior to 20 January 2023 (excluding vaccines). 71 out of the 882 newly added EMA drugs are only authorised by EMA, rather than from other regulatory bodies e.g.