Potential treatment with Chinese and Western medicine targeting NSP14 of SARS-CoV-2 / 药物分析学报

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious global health threat.This raises an urgent need for the devel-opment of effective drugs against the deadly disease.SARS-CoV-2 non-structural protein 14 (NSP14)carrying RNA cap guanine N7-methyltransferase and 3'-5'exoribonuclease activities could be a potential drug target for intervention.NSP14 of SARS-CoV-2 shares 98.7％ of similarity with the one (PDB 5NFY) of acute respiratory syndrome (SARS) by ClustalW.Then,the SARS-CoV-2 NSP14 structures were modelled by Modeller 9.18 using SARS NSP14 (PDB 5NFY) as template for virtual screening.Based on the docking score from AutoDock Vina1.1.2,18 small molecule drugs were selected for further evaluation.Based on the 5 ns MD simulation trajectory,binding free energy (AG) was calculated by MM/GBSA method.The calculated binding free energies of Saquinavir,Hypericin,Baicalein and Bromocriptine for the N-terminus of the homology model were-37.2711 ± 3.2160,-30.1746 ± 3.1914,-23.8953 ± 4.4800,and-34.1350 ± 4.3683 kcal/mol,respectively,while the calculated binding free energies were-60.2757 ± 4.7708,-30.9955 ± 2.9975,-46.3099 ± 3.5689,and-59.8104 ± 3.5389 kcal/mol,respectively,when binding to the C-terminus.Thus,the compounds including Saquinavir,Hypericin,Baicalein and Bromocriptine could bind to the N-terminus and C-terminus of the homology model of the SARS-CoV-2 NSP14,providing a candidate drug against SARS-CoV-2 for further study.

Genetic analysis of Penthorum chinense Pursh by improved RAPD and ISSR in China

Background: Penthorum chinense Pursh (P. chinense) is a well-known traditional Chinese medicine (TCM) plant, which has long been used for the prevention and treatment of hepatic diseases. This study aimed to genetically characterize the varieties of P. chinense from different geographic localities of China by random amplification of polymorphic DNA (RAPD)-PCR technique and verified with inter-simple sequence repeat (ISSR) markers. Results: The P. chinense samples were collected from nine different geographic localities. Previously improved RAPD and ISSR markers were utilized for genetic analysis using DNA amplification. The genetic relationship dendrogram was obtained by conducting cluster analysis to the similarity coefficient of improved RAPD and ISSR markers. Improved RAPD yielded 185 scorable amplified products, of which 68.6% of the bands were polymorphic, with an average amplification of 9.25 bands per primer. The ISSR markers revealed 156 alleles with 7.8 bands per primers, where 59.7% bands were polymorphic. Furthermore, the similarity coefficient ranges of RAPD and ISSR markers were 0.71­0.91 and 0.66­0.89, respectively. Conclusions: This study indicated that improved RAPD and ISSR methods are useful tools for evaluating the genetic diversity and characterizing P. chinense. Our findings can provide the theoretical basis for cultivar identification, standardization, and molecular-assisted breeding of P. chinense for medicinal use.

Identification of a New Lamin A/C Mutation in a Chinese Family Affected with Atrioventricular Block as the Prominent Phenotype / 华中科技大学学报（医学）（英德文版）

Even though mutations in LMNA have been reported in patients with typical dilated cardio-myopathy(DCM)and atrioventricular block(AVB)previously,the purpose of this study was to disclose this novel genetic abnormality in one Chinese family with the atypical phenotype of progressive AVB followed by DCM with normal QRS interval.Genome-wide linkage analysis mapped the AVB gene in this family to a marker at chromosome 1q21.2,where the LMNA gene was located.Direct DNA sequence analysis revealed a heterozygous G to A transition at nucleotide 244 in exon 1 of LMNA,which resulted in an E82K mutation.The E82K mutation co-segregated with all affected individuals in the family,and was not present in 200 normal controls.Further clinical evaluation of mutation carriers showed that 5 of 6 AVB patients exhibited mild DCM with a late onset of age in the fourth and fifth decades.Ejection fractions were documented in 5 patients with DCM,but 4 showed a normal value of ≥50%.Echocardiography showed that atrial dilatation occurred earlier than ventricular dilatation in the patients.This study suggests that progressive AVB with normal QRS interval and accompanying DCM at later stages may represent a distinct type of DCM.The molecular mechanism by which the E82K mutation causes AVB as the prominent phenotype in DCM may be a focus of future studies.