ABSTRACT
The World Health Organization (WHO) has declared the 2019 novel coronavirus (2019-nCoV) infection outbreak a global health emergency. Currently, there is no effective anti-2019-nCoV medication. The sequence identity of the 3CL proteases of 2019-nCoV and SARS is 96%, which provides a sound foundation for structural-based drug repositioning (SBDR). Based on a SARS 3CL protease X-ray crystal structure, we construct a 3D homology structure of 2019-nCoV 3CL protease. Based on this structure and existing experimental datasets for SARS 3CL protease inhibitors, we develop an SBDR model based on machine learning and mathematics to screen 1465 drugs in the DrugBank that have been approved by the U.S. Food and Drug Administration (FDA). We found that many FDA approved drugs are potentially highly potent to 2019-nCoV.
ABSTRACT
Bronchiolitis obliterans syndrome (BOS) is the main and late chronic complication after lung transplantation. It remains a major impediment to long-term outcome. Unfortunately, the survival rate of lung transplant recipients lags behind that of other organ transplant recipients, and BOS accounts for more than 30% of all mortality after the third year following lung transplantation. Most recent studies suggest that immune injury is the main pathogenic event in small airway obliteration and the development of BOS. Early detection of BOS is possible as well as essential because prompt initiation of treatment may halt the progress of the disease and the development of chronic graft failure. Current treatment of BOS is disappointing despite advances in surgical techniques and improvements in immunosuppressive therapies. Therefore, a clear understanding of the pathogenesis of BOS plays a major role in the search for new and effective therapeutic strategies for better long-term survival and quality of life after lung transplantation.
