As of March 3, 2021, several vaccines for COVID-19 showed good effectiveness in large-scale clinical studies and have been approved in many countries. However, any therapeutic drugs with sufficient efficacies have not been identified. While many proteins are proposed as anti-COVID-19 therapeutic drug targets, 3-chymotrypsin-like protease (3CLpro) is expected to be the most promising target because it is one of the main enzymes involved in replication of SARS-CoV-2 and the structure is relatively conserved among the coronavirus strains. In addition, NKG2A is also focused as an anti-COVID-19 drug target because NKG2A/CD94-HLA-E interaction increase the number of exhausted NK and T cells and suppress the elimination of SARS-CoV-2-infected cells.
Interprotein developed the following 4 strategies to block the onset of various symptoms of PCR-positive patients, accelerate the recovery from the symptom and/or decrease the death rate
- Identification of 3CLpro-targeting repurposing drug candidates (small molecules) by INTerprotein’s Engine for New Drug Design (INTENDD®), a structure-based drug discovery (SBDD) strategy, and/or artificial intelligence (AI)-guided INTENDD®, an AI-introduced activity prediction system.
- Drug discovery research for 3CLpro inhibitor (small molecules) based on the result of approach 1. by INTENDD® and/or AI-guided INTENDD®.
- Drug discovery research for NKG2A inhibitor by helix-loop-helix peptide (HLHP) technology, a new modality for the conformational-constrained therapeutic peptide.
- Potential assessment of curcumin and curcumin analogs/derivatives as anti-COVID-19 therapeutic drug.
In the approach 1., we proposed 21 repurposing drug candidates from 1741 approved drugs and identified 14 (67%) 3CLpro-binding compounds. Based on this result, we selected top 2 compounds and started drug discovery research for more potent compounds from those analogs/derivatives.