Progress on pharmacological mechanism of active components of Chinese materia medica on silicosis / 环境与职业医学

By the end of 2021, a total of 915000 cases of occupational pneumoconiosis and 450000 existing cases have been reported nationwide. Silicosis is a common and serious pneumoconiosis disease caused by long-term inhalation of large amounts of free silica dust and extensive nodular fibrosis in the lungs. Because its specific pathogenic mechanism has not been elucidated and the relevant research progress is slow, there is still a lack of effective therapeutic and interventional drugs. With the increase of national attention and the unique advantages of Chinese materia medica in the treatment of silicosis, more and more studies have been conducted on the treatment of silicosis with active ingredients of Chinese materia medica in China, but most of them are still in preclinical research stage. This article mainly introduced the pharmacological action and mechanism of selected active components of Chinese materia medica in the intervention of silicosis from three aspects: anti-inflammation, anti-oxidation, and intervention of apoptosis, providing ideas for subsequent research and development of new drugs for silicosis. This article argues, it is considered that some traditional Chinese medicines must observe the pathological changes in the treatment of silicosis in the overall animal experiment, clarify their pharmacodynamic effects, and further study the multiple targets and pathways involved in them to elucidate their specific mechanisms of action. At the same time, it can strengthen the analysis of active ingredients of traditional Chinese medicine, or modify the structure of active ingredients, and then enhance its pharmacological activity in the treatment of silicosis, realizing the transformation of preclinical research stage to the results of clinical research.

High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.