Oridonin Inhibits SARS-CoV-2 by Targeting Its 3C-Like Protease.

Oridonin Inhibits SARS-CoV-2 Oridonin, a natural product extracted from Rabdosia rubescens, possesses a wide range of pharmacological properties, including anti-inflammatory, anti-cancer, anti-microbial, neuroprotection, immunoregulation, etc. In article number 2100124, Baisen Zhong, Litao Sun, and co-workers demonstrate that Oridonin targets the SARS-CoV-2 3CL protease by covalently binding to cysteine145 in its active pocket to exert an anti-SARS-CoV-2 effect, which provides a novel candidate for the treatment of COVID-19.

Health risk assessment of perchlorate and chlorate in red swamp crayfish (Procambarus clarkii) in China.

Perchlorate and chlorate are both strong oxidants and thyroid toxicants that are widely distributed in soil, water and human foods. The red swamp crayfish (Procambarus clarkii) is a common aquatic organism that is popular in Chinese culinary dishes. Dietary intake is the main route of human exposure to perchlorate and chlorate, though the health risks of crayfish consumption are unknown. Thus, this study investigated the quantities of perchlorate and chlorate in red swap crayfish from sampling sites in five provinces located near the Yangtze River in China, along with the associated health risks of consuming this species. Perchlorate was detected in 55.6-100 % of crayfish samples in each sampling location, and chlorate was found in 100 % of samples cross all sites. Concentrations of perchlorate in crayfish from upstream provinces (Hubei, Hunan and Jiangxi) were higher than those from downstream provinces (Anhui and Jiangsu). Perchlorate and chlorate concentrations were positively correlated in crayfish, suggesting that chlorate may be a degradation byproduct of perchlorate. The quantities of both pollutants in hepatopancreas tissue were higher than in muscle tissues (p < 0.05), such that we do not recommend ingesting crayfish hepatopancreas. Hazard quotient (HQ) values for chlorate in crayfish were <1 across all provinces, suggesting no potential health risk of chlorate exposure through crayfish consumption. However, perchlorate concentrations in crayfish from the Jiangxi province had an associated HQ value >1, suggesting potential risks for human health. These results will be useful in informing mitigation measures aimed at reducing perchlorate exposure associated with crayfish consumption.

Oridonin Inhibits SARS-CoV-2 by Targeting Its 3C-Like Protease.

The current COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an enormous threat to public health. The SARS-CoV-2 3C-like protease (3CLpro), which is critical for viral replication and transcription, has been recognized as an ideal drug target. Herein, it is identified that three herbal compounds, Salvianolic acid A (SAA), (-)-Epigallocatechin gallate (EGCG), and Oridonin, directly inhibit the activity of SARS-CoV-2 3CLpro. Further, blocking SARS-CoV-2 infectivity by Oridonin is confirmed in cell-based experiments. By solving the crystal structure of 3CLpro in complex with Oridonin and comparing it to that of other ligands with 3CLpro, it is identified that Oridonin binds at the 3CLpro catalytic site by forming a C-S covalent bond, which is confirmed by mass spectrometry and kinetic study, blocking substrate binding through a nonpeptidomimetic covalent binding mode. Thus, Oridonin is a novel candidate to develop a new antiviral treatment for COVID-19.

Poly(ADP-ribose) polymerase-1 promotes expression of miR-155 by the up-regulation of methyl-CpG binding domain protein 2 in TK6 cells exposed to hydroquinone.

Hydroquinone (HQ), one of the major metabolites of benzene, can induce aberrant gene expression. MiR-155, a tumor activator, participates in various biological processes, including DNA damage response. However, the molecular mechanism of aberrant miR-155 expression is still not completely elucidated. Here, we investigated the mechanism of abnormal expression of miR-155 induced by poly(ADP-ribose)polymerase-1 (PARP-1) expression in HQ-treated TK6 lymphoblastoid cells. We examined the expression of genes related to abnormal expression of miR-155 to explore the reason for this phenomenon. The results of the present study showed that miR-155 was significantly increased and reactive oxygen species (ROS) were decreased in cells treated with HQ for 72 h compared with PBS-treated cells. Meanwhile, E4F1, PARP-1 and PARP-1 related co-regulators (NF-κB, HDAC1, and HDAC2), acetylated histone H3 (H3Ac) were increased in a concentration-dependent manner. Experiments for treatment with 5-AzaC (DNMTs inhibitor), TSA (HDACs inhibitor), DOX (to activate PARP-1) or MG132 (proteasome inhibitor) revealed that the MBDs and PARP-1 was positively associated with miR-155 expression. Moreover, in cells treated with HQ in conjunction with PARP-1 knockdown, expression of miR-155, H3Ac and MBD2 protein were decreased, compared with negative control. In conclusion, PARP-1 activates expression of miR-155 via acetylation by regulating MBD2 in TK6 cells exposed to HQ.