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.

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Background Robot-assisted minimally invasive surgery has shown tremendous advances over the traditional technique. However, currently commercialized systems are large and complicated, which vastly raises the system cost and operation room requirements.Methods A MIS robot named 'MicroHand' was developed over the past few years. The basic principle and the key technologies are analyzed in this paper. Comparison between the proposed robot and the da Vinci system is also presented. Finally, animal experiments were carried out to test the performance of MicroHand. ResultsFifteen animal experiments were carried out from July 2013 to December 2013. All animal experiments were finished successfully. ConclusionsThe proposed design method is an effective way to resolve the drawbacks of previous generations of the da Vinci surgical system. The animal experiment results confirmed the feasibility of the design. one was the assistant, and the third was the anesthesia surgeon. The main surgeon, without robotic surgery experience, had completed nearly 700 laparoscopic surgeries.The operations in all experiments complied with animal ethical standards. Each pig was in an ideal anesthetic state before surgery. Figure 15. Freeing the duct of the gall bladder 82 W. Wang et al.