Database Release 2021.4

Coronavirus

The Guide to Pharmacology coronavirus information page continues to be updated on a regular basis to capture the latest pharmacological strategies under investigation to mitigate against COVID-19.

Updates have most notably been made to the comments for molnupiravir (EIDD-2801, MK-4482). This followed its MHRA approval on 4th Nov 2021 as a treatment or recently diagnosed SARS-CoV-2 infection in non-hospitalised individuals who have at least one risk factor for developing severe illness.

Also add to the ligand list is PF-07321332, an oral SARS-CoV-2 3CL protease (Mpro) inhibitor, and clinical lead compound from Pfizer. It was progressed to clinical trial to determine safety and efficacy as a treatment for COVID-19. Phase 1 (NCT04756531) results were published in Science, in early November 2021 DOI: 10.1126/science.abl4784. A few days after the Phase 1 results were published, Pfizer announced that interim analysis from their Phase 3 EPIC-HR study (NCT04960202), indicated that PF-07321332 (in combination with ritonavir, as a formulation with the trade name Paxlovid) reduced the risk of hospitalisation or death by almost 90% in patients who were at high risk of progressing to severe illness, and who were treated within 3 days of symptom onset https://bit.ly/3wxA5of.

OAS1 (HGNC:8086; UniProt: P00973), an interferon-induced gene that is part of the innate antiviral defence system within host cells, has been added to the target table.

Curation Updates

Since our 2021.3 update we have added over ~110 new ligands. These have all been manually curated with chemical or peptide structures, links to external resources, general comments, notes on clinical development where appropriate, and target interaction data where this is available.

We have also made updates to ~46 existing ligand comments and ~52 clinical use comments. An additional 18 existing ligand have now been tagged as approved drugs, bringing the total approved drugs in GtoPdb to 1,716.

New Targets

5 new targets have been added to the database since the last release. These include HtrA serine peptidase 1, the target of galegenimab (Ph 2 geographic atrophy); heat shock protein family A (Hsp70) member 5, a potential therapeutic target for viral infections (incl. SARS-CoV-2), chemoresistant cancers and inflammation; coagulation factor III, tissue factor, the target of tisotumab vedotin (approved, oncology);clusterin: the target of sotevtamab (Ph 2 immunomodulator, antineoplastic); and transferrin receptor (CD71), which is exploited to improve site-specific drug delivery, including drug delivery across the blood-brain barrier e.g. pabinafusp alfa, lepunafusp alfa that deliver enzymes that are deficient in lysosomal storage disorders (both approved in Japan).

Website Updates

• The Guide to PHARMACOLOGY home-page has been revised, giving priority to the ways users can access the data. The site search and links to advanced search tools are more prominent. New panels link to ligand activity graphs, GtoImmuPdb, GtoMPdb, and current key resources. Page elements are more condensed to the top of the page and the site banner has been updated. 

Screenshot of the new GtoPdb home page. The site search is now more prominent, alongside the more advance search tools.

• New detailed endogenous ligand download file – this includes quantitative interaction data for endogenous pairings, along with the export of relevant comment fields.

Guide to Malaria Pharmacology (GtoMPdb)

These are the recent advancements made in the GtoMPdb for this database release:

• The Antimalarial targets family and the Antimalarial ligands family have been updated, giving a total of 40 P. falciparum (3D7) targets and 125 ligands tagged as antimalarial in the database.
• Work has continued on the process of adding subfamilies to the Antimalarial targets family.