Therapeutics and Small Molecules

Therapeutic treatments and drug-like small molecules.

Data classification:
Therapeutics: Molecules, drugs, antibodies, peptides, etc. which implement targets.
Targets: The biological mechanisms and functions which can be exploited to reduce, prevent, or treat the virus.
Proteins: The biological proteins associated with the SARS-CoV-2 virus and host.

Antibody

Immunoglobulin

Immunoglobulin AKA antibody is a protein produced by B cells that is used to fight against pathogens and viruses via adaptive immunity.

Mechanism: proposed to block viral Fc receptor activation by boosting endogenous neutralizing antibodies and preventing antibody-dependent enhancement of infection

Targeting Modalities: `Viral Fusion`

Known Protein Interactions: `Fc receptor`

Nivolumab

Nivolumab is a full human IgG4 antibody that targets PD-1, programmed cell death protein 1, and is used in combination with protease inhibitors to activate T-cells to launch an immune response against the tumor. Used to combat cancer

Mechanism: Blocks PD-1 inhibitory signaling to T-cells

Targeting Modalities: `Host Immune Response`

Known Protein Interactions: `PD-1`

Tocilizumab

targets soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R). Previously used for rheumatoid arthritis, systemic juvenile idiopathic arthritis, and CAR T cell induced severe or life threatening cytokine release syndrome in conjunction with protease inhibitors

Mechanism: Targets soluble and membrane-bound IL-6 receptors to decrease immune and inflammatory responses

Targeting Modalities: `Host Immune Response`

Known Protein Interactions: `IL6R`

Antiviral

Arbidol (Umifenovir)

Arbidol is an FDA approved drug for Influenza. Arbidol is an indole based antiviral/host-targeting agent.

Mechanism: May disrupt the binding of viral envelope protein to host cells and prevent viral entry to the target cell

Targeting Modalities: `Spike Binding` `Viral Replication` `Viral Fusion`

Known Protein Interactions: `ACE2` `spike`

Azvudine

Azvudine is an azidocytidine nucleoside analog. It is an reverse transcriptase inhibitor used in treatment of AIDS and Hepatitis C.

Mechanism: Blocks the reverse transcriptase enzyme halting the virus from replicating

Targeting Modalities: `Viral Replication`

Danoprevir

Danoprevir is a protease inhibitor used in combination with ritonavir for Hepatitis C and HIV-AIDS. Has been used in combination with ritonavir in SARS-2 patients.

Mechanism: Believed to inhibit the 3CL-PRO viral protease of SARS-CoV-2

Targeting Modalities: `Viral Replication`

Darunavir

Darunavir is an HIV protease inhibitor used in combination with pharmacokinetic enhancer like cobicistat.

Mechanism: Darunavir is an HIV protease inhibitor, but currently there is a lack of evidence of its utility in treating COVID-19.

Targeting Modalities: `Viral Replication`

Favipiravir

Favipiravir is a broad-spectrum antiviral used in treatment of influenza, ebola, and yellow fever. Favipiravir is a modified pyrazine analog.

Mechanism: Inhibits viral RNA-dependent RNA Polymerase

Targeting Modalities: `Viral Replication`

Known Protein Interactions: `RdRP`

Immunoglobulin

Immunoglobulin AKA antibody is a protein produced by B cells that is used to fight against pathogens and viruses via adaptive immunity.

Mechanism: proposed to block viral Fc receptor activation by boosting endogenous neutralizing antibodies and preventing antibody-dependent enhancement of infection

Targeting Modalities: `Viral Fusion`

Known Protein Interactions: `Fc receptor`

Interferons Alfa-2b

Interferons alfa-2b is a recombinant cytokine with antiviral or antineoplastic property. Interferons alfa-2b is used alone or in combination with lopinavir/ritonavir.

Mechanism: binds to type I interferon receptors (IFNAR1 and IFNAR2), upon dimerization activates two JAK tyrosine kinases, phosphorylate themselves and receptors then bind to Stat1 and Stat2 and activates multiple antiviral and immunomodulatory properties.

Targeting Modalities: `Viral Replication`

Immunotherapy

Immunoglobulin

Immunoglobulin AKA antibody is a protein produced by B cells that is used to fight against pathogens and viruses via adaptive immunity.

Mechanism: proposed to block viral Fc receptor activation by boosting endogenous neutralizing antibodies and preventing antibody-dependent enhancement of infection

Targeting Modalities: `Viral Fusion`

Known Protein Interactions: `Fc receptor`

Interferons Alfa-2b

Interferons alfa-2b is a recombinant cytokine with antiviral or antineoplastic property. Interferons alfa-2b is used alone or in combination with lopinavir/ritonavir.

Targeting Modalities: `Viral Replication`

Peptide

EK1C4

Pan-coronavirus fusion inhibitor EK1 peptide with GS linker and cholesterol. Show to be more effective against SARS-CoV-2

Mechanism:

Targeting Modalities: `Viral Fusion`

Known Protein Interactions: `spike` `S2` `fusion core` `HR1`

Immunoglobulin

Immunoglobulin AKA antibody is a protein produced by B cells that is used to fight against pathogens and viruses via adaptive immunity.

Mechanism: proposed to block viral Fc receptor activation by boosting endogenous neutralizing antibodies and preventing antibody-dependent enhancement of infection

Targeting Modalities: `Viral Fusion`

Known Protein Interactions: `Fc receptor`

Small Molecule

Chloroquine

Chloroquine is an aminoquinoline with anti-malarial and anti-inflammatory activities. Chloroquine acts during both viral entry and post entry steps.

Mechanism: The potential mechanisms for attacking the virus > By inhibiting viral enzymes, viral protein glycosylation, viral assembly, and virus release By changing the acidity of the cells By inhibiting the ACE2 cellular receptor By activating the immune response

Targeting Modalities: `Viral Replication` `Viral Fusion`

Known Protein Interactions: `ACE2` `spike`

Hydroxychloroquine

Hydroxychloroquine is primarily an antimalarial drugs alse used in treating autoimmune diseases like Rheumatoid arthritis, lupus. Hydroxychloroquine has more potency than chloroquine against SARS-CoV-2.

Mechanism: Act primarily by> Altering endosomal pH and affecting virus-cell fusion By inhibiting the ACE2 cellular receptor By activating the immune response

Targeting Modalities: `Viral Fusion` `Viral Replication`

Known Protein Interactions: `ACE2` `spike`

Lopinavir

Lopinavir is a protease inhibitor with high specificity for HIV-1 protease. It is used against HIV infections as a combinaton with Ritonavir (another protease inhibitor)

Mechanism: Inhibits the viral proteases

Targeting Modalities: `PLpro Protease Activity` `3CLpro Protease Activity`

Known Protein Interactions: `3CLpro` `PLpro`

Remdesivir

Remdesivir is a novel antiviral drug in the class of nucleotide analogs. Remdesivir is an adenosine analogue, which incorporates into nascent viral RNA chains and causes their pre-mature termination.

Mechanism: inhibitor of RNA-dependent RNA polymerase

Targeting Modalities: `Viral Replication`

Known Protein Interactions: `RdRP`

Therapeutics and Drug Databases

ANI-CAS Antiviral Archive

Description: The dataset files contain low-energy conformers and tautomers for 20,306 from the CAS Antiviral database. Original ~50K molecules were filtered for duplicates and drug-likeness. A collection consists of 67,167 tautomeric structures and ~6.6M conformers. After extensive sampling, for every tautomer we found low laying conformers within approx. 6 kcal/mol window using ANI-2x neural-network molecular potential. [DOI: 10.26434/chemrxiv.11819268.v1 ] The ANI-2x potential is approaching the accuracy of high-level QM calculations (wB97x-D). For each conformer we list total energy, relative energy, and dipole-consistent partial atomic charges. (~5.3GB zip file comprised of SDF files)

Lab: Olexandr Isayev Lab

ANI-FDA Drugs Archive

Description: The dataset files contain low-energy conformers and tautomers of 6,433 FDA approved & investigational drugs. A collection consists of 32,036 tautomeric structures and ~3M conformers. After extensive sampling, for every tautomer we found low laying conformers within approx. 6 kcal/mol window using ANI-2x neural-network molecular potential. The ANI-2x potential is approaching the accuracy of high-level QM calculations (wB97x-D). [DOI: 10.26434/chemrxiv.11819268.v1 ] For each conformer we list total energy, relative energy, and dipole-consistent partial atomic charges. (~2.1GB zip file comprised of SDF files)

Lab: Olexandr Isayev Lab

Drug Repurposing Hub

Description: The Drug Repurposing Hub is a curated and annotated collection of FDA-approved drugs, clinical trial drugs, and pre-clinical tool compounds with a companion information resource. Order library plates to screen yourself or collaborate with the Broad Institute’s Center for the Development of Therapeutics to see if an existing drug may work against your novel target, model system, or indication. While the collection will undoubtedly reveal new uses for developed drugs, its true power is unlocked when applied to discover new biological insights and disease mechanisms.

Institution: University of California, San Francisco

Lab: John Irwin, Brian Shoichet, and others

DrugBank Database

Description: The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug data with comprehensive drug target information.

Institution: University of Alberta and The Metabolomics Innovation Centre

Lab: David Wishart

MolPort

Description: MolPort has collected the catalogs of all the major chemical suppliers that cater to drug discovery and created a consolidated database of commercially available screening compounds, building blocks and virtual compounds. These catalogs are up to date and typically synchronized with suppliers inventory daily. MolPort tracks compounds ordered via its platform, and monitors how well suppliers fulfil orders.

Organization: MolPort, Inc.

Open Science Data Portal

Description: NCATS is generating a collection of datasets by screening a panel of SARS-CoV-2-related assays against all approved drugs. These datasets, as well as the assay protocols used to generate them, are being made immediately available to the scientific community on this site as these screens are completed.

Organization: National Center for Advancing Translational Sciences (NCATS)

Institution: National Institutes of Health

Enamine REAL Space

Description: The REAL Space comprises 13 billion make-on-demand molecules and is currently the largest offer of commercially available compounds. The REAL compounds in the Space are assembled via more than 180 well-validated parallel synthesis protocols applied to over 115 000 qualified reagents and building blocks. The synthetic protocols include standard and advanced one-pot procedures. They differ in the number of steps, type of purification, and compound handling, and therefore in the effort required to deliver the products.

Organization: Enamine Ltd

SuperDRUG

Description: SuperDRUG2 database is a unique, one-stop resource for approved/marketed drugs, containing more than 4,600 active pharmaceutical ingredients. We annotated drugs with regulatory details, chemical structures (2D and 3D), dosage, biological targets, physicochemical properties, external identifiers, side-effects and pharmacokinetic data. Different search mechanisms allow navigation through the chemical space of approved drugs. A 2D chemical structure search is provided in addition to a 3D superposition feature that superposes a drug with ligands already known to be found in the experimentally determined protein-ligand complexes.

Institution: University Medicine Berlin

Lab: Structural Bioinformatics Group

SWEETLEAD

Description: The SWEETLEAD database is a cheminformatics database of medicines, drugs, and herbal isolates. It provides a resource for chemical structures and was built by pulling data from several public chemical databases.

Lab: Paul Novick and Vijay Pande

WuXi GalaXi

Description: The first version of this new chemical space approaches 2 billion tangible molecules — 1,686,371,588 (or 1,7*109) to be exact. In close collaboration with WuXi LabNetwork we created a novel chemical space ready for you to download and search. This space contains a lot of unique chemical intellectual property (IP) for your research, and compounds can be created on demand upon request with WuXi. GalaXi has been shaped from WuXi LabNetwork’s building blocks and reaction schemes that have been properly checked to deliver high quality results. High quality processing has been ensured using our CoLibri software.

Organization: BioSolveIT, WuXi LabNetwork

Zinc15 Database

Description: Database of commercially-available compounds for virtual screening. ZINC contains over 230 million purchasable compounds in ready-to-dock, 3D formats. ZINC also contains over 750 million purchasable compounds you can search for analogs in under a minute.

Institution: University of California, San Francisco

Lab: John Irwin, Brian Shoichet, and others