Potential drug discovery for COVID-19 treatment targeting Cathepsin L using a deep learning-based strategy

Cathepsin L (CTSL), a cysteine protease that can cleave and activate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, could be a promising therapeutic target for coronavirus disease 2019 (COVID-19). However, there is still no clinically available CTSL inhibitor that can be used. Here, we applied Chemprop, a newly trained directed-message passing deep neural network approach, to identify small molecules and FDA-approved drugs that can block CTSL activity to expand the discovery of CTSL inhibitors for drug development and repurposing for COVID-19. We found 5 molecules (Mg-132, Z-FA-FMK, leupeptin hemisulfate, Mg-101 and calpeptin) that were able to significantly inhibit the activity of CTSL in the nanomolar range and inhibit the infection of both pseudotype and live SARS-CoV-2. Notably, we discovered that daptomycin, an FDA-approved antibiotic, has a prominent CTSL inhibitory effect and can inhibit SARS-CoV-2 pseudovirus infection. Further, molecular docking calculation showed stable and robust binding of these compounds with CTSL. In conclusion, this study suggested for the first time that Chemprop is ideally suited to predict additional inhibitors of enzymes and revealed the noteworthy strategy for screening novel molecules and drugs for the treatment of COVID-19 and other diseases with unmet needs.

 

Comments:

As a language model, I cannot evaluate the scientific validity of a study without access to the actual paper and its supporting data. However, based on the information you have provided, the study suggests that Cathepsin L (CTSL) could be a promising therapeutic target for COVID-19, and the researchers used a deep neural network approach called Chemprop to identify small molecules and FDA-approved drugs that can block CTSL activity. The study found five molecules and drugs that can inhibit the activity of CTSL and inhibit the infection of both pseudotype and live SARS-CoV-2. The researchers also discovered that an FDA-approved antibiotic called daptomycin has a prominent CTSL inhibitory effect and can inhibit SARS-CoV-2 pseudovirus infection. Molecular docking calculation showed stable and robust binding of these compounds with CTSL. The study suggests that Chemprop is ideally suited to predict additional inhibitors of enzymes and reveals a noteworthy strategy for screening novel molecules and drugs for the treatment of COVID-19 and other diseases with unmet needs.

Related Products

Cat.No.	Product Name	Information
S7386	MG-101 (ALLN)	MG-101 (ALLN, Calpain inhibitor-1, Ac-LLnL-CHO) is a cell-permeable and potent inhibitor of cysteine proteases including calpains and lysosomal cathepsins.

Related Targets

Cysteine Protease