Caution: None of  the compounds here are intended for human consumption. These are compounds for researchers and experimental investigations by the scientific community.

 

Introduction

We have carried out a large number of ultra-large virtual screens against 17 important SARS-CoV-2 proteins, covering a total of 40 different sites among those 17 proteins. 

The drug discovery platform which we have used is VirtualFlow.

We are making available the following datasets:

  • An interactive table (for ultra-large virtual screen) containing the top 1000 hits. This interactive table allows to
    • interactively filter the hits
    • see important properties of each hit
    • follow the link to the original catalog/or vendor of the compound
    • visually explore the virtual hits in a 3D molecular viewer (Mol*) docked to the receptor structure
  • The top 1 million hits (i.e. the top ~0.1 % of the virtual hits) downloadable as molecular database files (in the free DataWarrior format)
  • Special datasets, such as lists of world-approved drugs among the virtual hits

To cite our work, please reference 

A commercial service for ultra-large virtual screenings based on VirtualFlow is available via the company Virtual Discovery, Inc.

Targeted Protein Sites

We targeted a total of 40 different sites among 17 critical proteins related to SARS-CoV-2. For a few of these target sites, we have carried out more than one virtual screen (using different receptor structures). 

ACE2 - Site 1 - Spike Binding Interface
ACE2 - Site 1 - Spike Binding Interface
The angiotensin-converting enzyme 2 (ACE2) receptor plays a keyrole in the entry process of the virus into human cells. We have targeted a site (around residue Glu37) with two virtual screens (Screen IDs 1 and 2).
ACE2 - Site 2 - Spike Binding Interface
ACE2 - Site 2 - Spike Binding Interface
The angiotensin-converting enzyme 2 (ACE2) receptor plays a keyrole in the entry process of the virus into human cells. We have targeted a site (around residue Gly354) with one virtual screen (Screen ID 3).
ACE2 - Site 3 - Nearby Spike Binding Interface
ACE2 - Site 3 - Nearby Spike Binding Interface
The angiotensin-converting enzyme 2 (ACE2) receptor plays a keyrole in the entry process of the virus into human cells. We have targeted a dynamic pocket with one virtual screen (Screen ID 4).
ACE2 - Site 4 - Nearby Spike Binding Interface
ACE2 - Site 4 - Nearby Spike Binding Interface
The angiotensin-converting enzyme 2 (ACE2) receptor plays a keyrole in the entry process of the virus into human cells. We have targeted a second dynamic pocket with one virtual screen (Screen ID 5)
TMPRSS2 - Active Site
TMPRSS2 - Active Site
The essential priming of S during entry can be executed by the host serine protease TMPRSS2 in the case of SARS-CoV-2, making it a potential therapeutic target. In addition, recent research has shown that the TMPRSS2 inhibtor, camostat mesylate, can block viral entry in cell-based assays. We have targeted the active site of TMPRSS2 (Screen ID 6).
Spike Protein - ACE2 Binding Site
Spike Protein - ACE2 Binding Site
The spike protein forms the highly glycosylated trimeric receptor-binding protein that decorates the virion surface and facilitates entry into the host cell through interaction with its receptor ACE2. We have targeted the ACE2 binding interface on the RBD of the spike protein via an ultra-large virtual screen (Screen ID 7).
Spike Protein - HR1 Domain - HR2 Binding Interface
Spike Protein - HR1 Domain - HR2 Binding Interface
The HR domains of the spike protein and their mode of interaction are known to be of critical importance, and are highly conserved across corona viruses, making them an attractive target for the development of pan-coronavirus fusion inhibitors. We have targeted the HR2 binding interface of the HR1 domain.
ORF7a - Entire Surface (Blind Docking)
ORF7a - Entire Surface (Blind Docking)
ORF7a is an accessory protein with a transmembrane helix at the C-terminus that is known to localize to the ER, Golgi, and cell surface. The assembly of ORF7a into viral particles suggests that the protein is important in the viral replication cycle, and that it might have a function early on in the infection. We have carried out a blind docking against the entire surface (Screen ID 8).
nsp3 - Macrodomain - Active Site
nsp3 - Macrodomain - Active Site
The macrodomain, sometimes also called the X domain, is a highly conserved region of ~180 amino acids that binds to ADP ribose, which has been shown to have possible roles in evading host innate immune response. We have targeted the active site of the macrodomain (Screen IDs 10 and 11).
nsp3 - PLpro - Active Site
nsp3 - PLpro - Active Site
PLpro is a critical protease of the SARS-CoV-2 virus. PLpro also possesses deubiquitination and de-ISGylation activity that aids in the disruption of the interferon regulatory factor 3 (IRF3) pathway and host innate immune responses. Here we have targeted the active site of PLpro (Screen IDs 12, 15).
nsp3 - PLpro - Accessory Pocket
nsp3 - PLpro - Accessory Pocket
PLpro is a critical protease of the SARS-CoV-2 virus. Here we have targeted the accessory pocket of PLpro (Screen ID 13), which is located directly besides the enzymatic active site and known to have the ability to inhibit the enzymatic activity when drugged with small molecules.
nsp3 - PLpro - DUB Binding Site
nsp3 - PLpro - DUB Binding Site
PLpro is a critical protease of the SARS-CoV-2 virus. PLpro also possesses deubiquitination and de-ISGylation activity that aids in the disruption of the interferon regulatory factor 3 (IRF3) pathway and host innate immune responses. Here we have targeted the DUB binding site of PLpro (Screen ID 14).
nsp5 (Mpro) - Active Site
nsp5 (Mpro) - Active Site
Mpro, the main protease of coronavirus, cleaves PP1a and PP1ab into many of their constituent nsps (11 cleavage sites in PP1ab). The inhibition of Mpro would not only inhibit the protease itself, but also hinder downstream processes by preventing the production of key viral proteins through inhibition of their proteolytic processing. Here we targeted the active site or Mpro (Screen IDs 16, 17).
nsp5 (Mpro) - Dimerization Site
nsp5 (Mpro) - Dimerization Site
Mpro, the main protease of coronavirus, cleaves PP1a and PP1ab into many of their constituent nsps (11 cleavage sites in PP1ab). Mpro is a functional dimer, meaning it does not have any significant activity when it is not in dimer form. We have targeted the dimerization interface of Mpro (Screen ID 18).


nsp5 (Mpro) - Alpha Helix 5 Association Site
nsp5 (Mpro) - Alpha Helix 5 Association Site
Mpro, the main protease of coronavirus, is a functional dimer. Meaning it does not have any significant activity when it is not in dimer form. The dimer can only form when the alpha helix 5 helix is associated to the main part of Mpro. We have targeted the alpha helix 5 binding site (Screen ID 19).
NSP7 - Entire Surface (Blind Docking)
nsp7 - Entire Surface (Blind Docking)
nsp7 forms a complex with nsp12 and nsp8, which gives rise to a large multi-protein assembly capable of nucleotide polymerization with additional nsps playing important roles in RNA modification. Here we targeted the surface of nsp7 via a blind docking based screening (Screen ID 20).
nsp8 - nsp7 Binding Interface
nsp8 - nsp7 Binding Interface
nsp8 forms a complex with nsp12 and nsp8, which gives rise to a large multi-protein assembly capable of nucleotide polymerization with additional nsps playing important roles in RNA modification. Here we targeted the nsp7 binding site on nsp8 (Screen ID 21).
nsp8 - nsp12 Binding Interface
nsp8 - nsp12 Binding Interface
nsp8 forms a complex with nsp12 and nsp8, which gives rise to a large multi-protein assembly capable of nucleotide polymerization with additional nsps playing important roles in RNA modification. Here we targeted the nsp12 binding site on nsp8 (Screen ID 22).
nsp9 - Dimerization Interface - Site 1
nsp9 - Dimerization Interface - Site 1
nsp9 is known to co-localize with nsp7, nsp8 and nsp10 within the replication complex and is presumed to play a role in RNA replication. Since dimerization has been found to be essential for viral replication, we have targeted the a site on the dimerization interface as a method of inhibiting viral replication (screen ID 23).
nsp9 - Dimerization Interface - Site 2
nsp9 - Dimerization Interface - Site 2
nsp9 is known to co-localize with nsp7, nsp8 and nsp10 within the replication complex and is presumed to play a role in RNA replication. Since dimerization has been found to be essential for viral replication, we have targeted the a second site on the dimerization interface as a method of inhibiting viral replication (screen ID 24).
nsp10 - Site 1 - nsp14/nsp16 Binding Interface
nsp10 - Site 1 - nsp14/nsp16 Binding Interface
The binding of nsp10 to nsp14 and nsp16 is critical for the functioning of both enzymes, which play an important role in several aspects of the virus life cycle. Therefore we have targeted the shared binding interface of nsp16 and nsp14 on nsp10 (Screen IDs 25 and 26).
nsp10 - Site 2 - nsp14 Binding Interface
nsp10 - Site 2 - nsp14 Binding Interface
The binding of nsp10 to nsp14 is critical for the functioning of this enzyme, which play an important role for the virus in several ways. Therefore we have targeted the binding interface of nsp14 (Screen ID 27), at a region which is shared with the nsp16 binding interface.
RdRp (nsp12) - RNA Binding Site 1
RdRp (nsp12) - RNA Binding Site 1
The RdRP (nsp12) forms a complex with nsp12 and nsp8, which gives rise to a large multi-protein assembly capable of nucleotide polymerization with additional nsps playing important roles in RNA modification. Here we targeted an RNA binding site on nsp12 (Screen ID 28).
RdRp (nsp12) - RNA Binding Site 2
RdRp (nsp12) - RNA Binding Site 2
The RdRP (nsp12) forms a complex with nsp12 and nsp8, which gives rise to a large multi-protein assembly capable of nucleotide polymerization with additional nsps playing important roles in RNA modification. Here we targeted a second RNA binding site of nsp12 (Screen ID 29).
RdRp (nsp12) - Nucleotide Binding Site
RdRp (nsp12) - Nucleotide Binding Site
The RdRP (nsp12) forms a complex with nsp12 and nsp8, which gives rise to a large multi-protein assembly capable of nucleotide polymerization with additional nsps playing important roles in RNA modification. Here we targeted the nucleotide binding site of nsp12 (Screen ID 30).
RdRp (nsp12) - nsp8 Binding Interface
RdRp (nsp12) - nsp8 Binding Interface
The RdRP (nsp12) forms a complex with nsp12 and nsp8, which gives rise to a large multi-protein assembly capable of nucleotide polymerization with additional nsps playing important roles in RNA modification. Here we targeted the nsp8 binding site on nsp12 (Screen ID 31).
RdRp (nsp12) - nsp7 Binding Site
RdRp (nsp12) - nsp7 Binding Site
The RdRP (nsp12) forms a complex with nsp12 and nsp8, which gives rise to a large multi-protein assembly capable of nucleotide polymerization with additional nsps playing important roles in RNA modification. Here we targeted the nsp7 binding site on nsp12 (Screen ID 32).
nsp13 - Active Site
Helicase - Active Site
nsp13, which is one of the few proteins that is fully conserved in SARS-CoV and SARS-CoV-2, has known activity as an RNA helicase, NTPase, dNTPase, RTPase, and DNA helicase. It is also known to interact with nsp12. Here, we are targeting the active site of the helicase (Screen ID 33).
Helicase - RNA Binding Site 1
Helicase - RNA Binding Site 1
nsp13, which is one of the few proteins that is fully conserved in SARS-CoV and SARS-CoV-2, has known activity as an RNA helicase, NTPase, dNTPase, RTPase, and DNA helicase. It is also known to interact with nsp12. Here, we are targeting the a site on the RNA binding interface on the helicase (Screen ID 34).
Helicase - RNA Binding Site 2
Helicase - RNA Binding Site 2
nsp13, which is one of the few proteins that is fully conserved in SARS-CoV and SARS-CoV-2, has known activity as an RNA helicase, NTPase, dNTPase, RTPase, and DNA helicase. It is also known to interact with nsp12. Here, we are targeting the a second site on the RNA binding interface on the helicase (Screen ID 35).
nsp14 (ExoN, N7-MTase) - nsp10 Binding Interface
nsp14 (ExoN, N7-MTase) - nsp10 Binding Interface
nsp14 is critical for viral replication and transcription, as it plays dual roles in proofreading and mRNA capping. Disruption of nsp14 exonuclease activity has been shown to result in increased sensitivity of the virus to Ribavirin (RBV) and 5-fluorouracil (5-FU), demonstrating the importance of this 3'-mismatched dsRNA excision activity. Here, we are targeting the nsp10 binding interface on nsp14 (Screen ID 36), which is critical for the ExoN enzymatic activity.
nsp14 (ExoN, N7-MTase) - ExoN Active Site
nsp14 (ExoN, N7-MTase) - ExoN Active Site
nsp14 is critical for viral replication and transcription, as it plays dual roles in proofreading and mRNA capping. Disruption of nsp14 exonuclease activity has been shown to result in increased sensitivity of the virus to Ribavirin (RBV) and 5-fluorouracil (5-FU), demonstrating the importance of this 3'-mismatched dsRNA excision activity. Here, we are targeting the active site of the ExoN domain (Screen ID 37).

nsp14 (ExoN, N7-MTase) - N7-MTase Active Site
nsp14 (ExoN, N7-MTase) - N7-MTase Active Site
nsp14 is critical for viral replication and transcription, as it plays dual roles in proofreading and mRNA capping. nsp14 also functions as a SAM-dependent guanine-N7 methyltrasferase (N7-MTase). Mutation studies in a replicon system have shown that this N7-MTase activity is critical for viral replication and transcription. Here, we are targeting the active site of the N7-MTase domain (Screen ID 38).
nsp15 (XendoU) - Active Site
nsp15 (XendoU) - Active Site
nsp15 is a uridylate-specific endoribonuclease (NendoU) carrying a C-terminal catalytic EndoU domain that has been described as having various roles in immune evasion in different coronviruses. We have targeted the active site of this enzyme (Screen ID 39).


nsp16 (2′-O-MTase) - Active Site
nsp16 (2′-O-MTase) - Active Site
RNA cap modifications are known to play a role in the host cell's identification of self-RNA. For example, foreign RNA which lacks 2'-O methylation is inhibited by IFIT1. Here we have targeted the active site of this enzyme (Screen ID 41).
nsp16 (2′-O-MTase) - nsp10 BInding Interface
nsp16 (2′-O-MTase) - nsp10 BInding Interface
RNA cap modifications are known to play a role in the host cell's identification of self-RNA. For example, foreign RNA which lacks 2\textquotesingle -O methylation is inhibited by IFIT1. nsp16 requires the binding of nsp10 to perform it's function. Here we targeted the nsp10 binding site on nrp16 (Screen ID 40).
Nucleoprotein (N) - NTD RNA Binding Interface
Nucleoprotein (N) - NTD RNA Binding Interface
Nucleocapsid protein (N) forms large oligomeric complexes with the replicated viral genome. The resulting ribonucleoprotein (RNP) complexes associate with M, facilitating packaging of the genome into a complete virion assembly. Here we have targeted the RNA binding site of the N-terminal domain (Screen ID 42).
Nucleoprotein (N) - NTD Oligomerization Interface
Nucleoprotein (N) - NTD Oligomerization Interface
Nucleocapsid protein (N) forms large oligomeric complexes with the replicated viral genome. The resulting ribonucleoprotein (RNP) complexes associate with M, facilitating packaging of the genome into a complete virion assembly. Here we have targeted the oligomerization site of the N-terminal domain (Screen ID 43).
Nucleoprotein (N) - CTD Dimerization Interface
Nucleoprotein (N) - CTD Dimerization Interface
Nucleocapsid protein (N) forms large oligomeric complexes with the replicated viral genome. The resulting ribonucleoprotein (RNP) complexes associate with M, facilitating packaging of the genome into a complete virion assembly. Here we have targeted the dimerization site of the C-terminal domain (Screen ID 44).
Nucleoprotein (N) - CTD Oligomerization Interface
Nucleoprotein (N) - CTD Oligomerization Interface
Nucleocapsid protein (N) forms large oligomeric complexes with the replicated viral genome. The resulting ribonucleoprotein (RNP) complexes associate with M, facilitating packaging of the genome into a complete virion assembly. Here we have targeted the oligomerization interface of the dimerized C-terminal domain (Screen ID 45).

Special Compound Sets

Some of the virtual hits belong to special classes of compounds, such as the approved drugs or natural products. Here, we make some of the special sets available. 

 

Caution: None of  the compounds here are intended for human consumption. These are compounds for researchers and experimental investigations by the scientific community.

World Approved Drugs
World Approved Drugs
Hits from our virtual screens which are approved in at least one country, such as the USA.
Investigational Drugs
Investigational Drugs
Hits from our virtual screenings which are investigational compounds (i.e. have been part of clinical studies).
In-Man Compounds
In-Man Compounds
Hits from our virtual screens which are in-man compounds, i.e. compounds which were in humans, e.g nutriceuticals and many metabolites (but not investigational or approved drugs).
Natural Products
Natural Products
Hit compounds from our virtual screenings which are natural products