Coronavirus causes a disease with high infectivity and pathogenicity, especially SARS in 2003, MERS in 2012, and COVID-2019 currently. The spike proteins of these coronaviruses are critical for host cell entry by receptors. Thus, searching for broad-spectrum anti-coronavirus candidates, such as spike protein inhibitors, is vital and desirable due to the mutations in the spike protein. In this study, a combination of computer-aided drug design and biological verification was used to discover active monomers from traditional Chinese medicine. Surface plasmon resonance (SPR) assays and NanoBit assays were used to verify the predicated compounds with their binding activities to spike proteins and inhibitory activities on the SARS-CoV-2 RBD/ACE2 interaction, respectively. Furthermore, an MTT assay was used to evaluate the cell toxicities of active compounds. As a result, glycyrrhizic acid ( ZZY-44 ) was found to be the most efficient and nontoxic broad-spectrum anti-coronavirus molecule in vitro , especially, the significant effect on SARS-CoV-2, which provided a theoretical basis for the study of the pharmacodynamic material basis of traditional Chinese medicine against SARS-CoV-2 and offered a lead compound for further structural modification in order to obtain more effective candidate drugs against SARS-CoV-2.

ClinicalTrials.gov: NCT02479581.

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Two tunable arylative cyclizations of cyclohexadienone-containing 1,6-enynes are reported via rhodium(III)-catalyzed C-H activation of O-substituted N-hydroxybenzamides. The use of different O substituents, i.e. O-Piv and O-Me, on the directing group allows the formation of either tetracyclic isoquinolones through an Ⓝ-Michael addition process or hydrobenzofurans through a Ⓒ-Michael addition process. Mechanistic investigations of these two cascade reactions clearly indicated that the C-H bond cleavage process was involved in the turnover-limiting step. Furthermore, the cyclization products could be subjected to various transformations for elaborating the pharmaceutically and synthetically valuable potential. This is the first example of a rhodium(III)-catalyzed arylative cyclization reaction of 1,6-enynes, and the results extend the application realm of Cp*Rh(III)-catalyzed C-H activation cascade reactions.

The present study demonstrated that postconditioning may protect adult myocardium undergoing cold blood cardioplegic arrest. These data support the need for a further clinical trial of postconditioning in cardiac surgery.

[reaction: see text] An efficient method for the highly diastereoselective synthesis of chiral homoallylic amines by Zn-mediated allylation of chiral N-tert-butanesulfinyl imines at room temperature was developed. By simply tuning the reaction conditions, the method allows the achievement of a highly remarkable opposite stereocontrol, affording the desired stereochemical outcome in good yield and with excellent diastereoselectivity (up to 98% dr). With N-sulfinyl ketimines, the corresponding quaternary carbon-containing chiral homoallylic amines could also be produced.

Fontan procedure. Therefore, the sequence of events is consistent with the hypothesis that the increase in PA pressure may have been caused by obstructive tonsillar hypertrophy and was thereby reversed after tonsillectomy in this patient.Tonsillar hypertrophy is a common cause of OSA in children. Moderate-to-severe OSA is frequently associated with mild pulmonary hypertension, 3 which is characterized by mild pulmonary vascular remodeling and endothelial dysfunction, as shown in human and animal studies. 4,5 Therefore, it is possible that the magnitude of structural and functional alterations in pulmonary vasculature induced by nocturnal desaturation had significant impacts on the Glenn circulation, and that these changes were reversed after tonsillectomy in this case. Furthermore, it is interesting to speculate that such derangement in pulmonary circulation caused by OSA might have similar effects on hemodynamics in patients even after the Fontan procedure. This unique case implies that alleviation of OSA (ie, tonsillectomy) may be an efficacious treatment option for high-risk candidates for the Fontan procedure with high PA pressure after the Glenn procedure.

Myricetin is a widely distributed bioactive flavonoid with scientific interest attributed to its anti-oxidant, antitumor, and anti-inflammatory properties. A specific and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated for identification and quantification of myricetin in rat plasma after oral and intravenous administrations. Kaempferol was used as an internal standard. Followed by β-glucuronidase and sulfatase hydrolysis and liquid-liquid extraction with ethyl acetate, the analytes were separated on an Acquity UPLC BEH C18 column (2.1×50 mm, 1.7 μm) and analyzed in the selected ion recording with a negative electrospray ionization mode. The developed method was validated for selectivity, accuracy, precision, linearity, recovery, stability and matrix effect. The assay was validated over a wide concentration range of 2-4,000 ng/mL. Intra- and inter-day precisions were all less than 13.49% and accuracy ranged from 95.75 to 109.80%. The present method was successfully applied to investigate a pharmacokinetic study of myricetin following intravenous and oral administrations to rats. The absolute bioavailability was found to be 9.62% and 9.74% at 2 oral doses (50 mg/kg and 100 mg/kg, respectively), which indicated myricetin was poorly absorbed after oral administration. To our knowledge, this is the first pharmacokinetic evaluation of myricetin as a single active pharmaceutical ingredient in preclinical studies.