Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and there is no cure currently. The 3CL protease (3CLpro) is a highly conserved protease which is indispensable for CoVs replication, and is a promising target for development of broad-spectrum antiviral drugs. In this study we investigated the anti-SARS-CoV-2 potential of Shuanghuanglian preparation, a Chinese traditional patent medicine with a long history for treating respiratory tract infection in China. We showed that either the oral liquid of Shuanghuanglian, the lyophilized powder of Shuanghuanglian for injection or their bioactive components dose-dependently inhibited SARS-CoV-2 3CLpro as well as the replication of SARS-CoV-2 in Vero E6 cells. Baicalin and baicalein, two ingredients of Shuanghuanglian, were characterized as the first noncovalent, nonpeptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography was distinctly different from those of known 3CLpro inhibitors. Baicalein was productively ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a “shield” in front of the catalytic dyad to effectively prevent substrate access to the catalytic dyad within the active site. Overall, this study provides an example for exploring the in vitro potency of Chinese traditional patent medicines and effectively identifying bioactive ingredients toward a specific target, and gains evidence supporting the in vivo studies of Shuanghuanglian oral liquid as well as two natural products for COVID-19 treatment.

Three new coumarins containing a C 10 terpenoid side chain, clauslactones R-T (1-3), together with 14 known coumarins (4-17) and 11 known carbazole alkaloids (18-28), were isolated from the leaves and stems of Clausena excavata. Their structures were established by detailed spectroscopic analyses. Furthermore, the stereochemistry of 1 was confirmed by single-crystal X-ray diffraction analysis, which was the first example among coumarins with a C 10 terpenoid side chain. Additionally, compounds 22 and 27 were found to show moderate topoisomerase II inhibitory effects at 50 m mM.

Vaccinium bracteatum Thunb. (Ericaceae), known as "Nan Zhu" in Chinese, is an evergreen shrubby tree distributed in mountainous regions of southern China and recognized as an edible and also a medicinal product for use in daily life. Its fruits ("Nan Zhu Zi"), like cranberry and blueberry, can be used as a fruit or beverage material. Its leaves have been used for cooking since the Tang Dynasty, and now it has been a tradition to eat this kind of food during the "Qing Ming Festival" in the south of China. As V. bracteatum was reported to possess significant health benefits, such as antifatigue, antianemia, antioxidant and immunomodulate effects, 1 an array of phytochemical investigations have been conducted, revealing the existence of fatty acids, flavonoids and triterpenes as the main chemical components. 2,3 Iridoid glucosides have also been reported as one type of minor constitutes from this plant. [4][5][6]