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https://www.selleckchem.com/products/gi254023x.html 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. This article examines whether perceptions of supportive work-life culture changed during the COVID-19 pandemic-and if that depended on (1) working from home; (2) children in the household; and (3) professional status. We test for gender differences across the analyses. During normal times, the "ideal worker" is expected to prioritize the demands of their job and is penalized for attending to family/personal needs while on company time. But the organization and expectations of roles might have changed due to the COVID-19 pandemic. Organizations could have become more empathic or reinforced
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