ABSTRACT
OBJECTIVES@#This study aims to explore the therapeutic targets of curcumin in periodontitis through network pharmacology and molecular docking technology.@*METHODS@#Targets of curcumin and periodontitis were predicted by different databases, and the protein-protein interaction (PPI) network constructed by String revealed the interaction between curcumin and periodontitis. The key target genes were screened for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was performed to analyze the binding potential of curcumin to periodontitis.@*RESULTS@#A total of 672 periodontitis-related disease targets and 107 curcumin-acting targets were obtained from the databases, and 20 key targets were screened. The GO and KEGG analyses of the 20 targets showed that curcumin might play a therapeutic role through the hypoxia-inducible factor (HIF)-1 and parathyroid hormone (PTH) signaling pathways. Molecular docking analysis showed that curcumin had good binding potential with multiple targets.@*CONCLUSIONS@#The potential key targets and molecular mechanisms of curcumin in treating periodontitis provide a theoretical basis for new drug development and clinical applications.
Subject(s)
Humans , Network Pharmacology , Curcumin/therapeutic use , Molecular Docking Simulation , Periodontitis/drug therapy , Drugs, Chinese Herbal , Medicine, Chinese TraditionalABSTRACT
Although human antibodies elicited by severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-directed antibodies. Herein, we isolated and profiled a panel of 32 N protein-specific monoclonal antibodies (mAb) from a quick recovery coronavirus disease-19 (COVID-19) convalescent, who had dominant antibody responses to SARS-CoV-2 N protein rather than to Spike protein. The complex structure of N protein RNA binding domain with the highest binding affinity mAb nCoV396 reveals the epitopes and antigens allosteric changes. Functionally, a virus-free complement hyper-activation analysis demonstrates that nCoV396 specifically compromises N protein-induced complement hyper-activation, a risk factor for morbidity and mortality in COVID-19, thus paving the way for functional anti-N mAbs identification. One Sentence SummaryB cell profiling, structural determination, and protease activity assays identify a functional antibody to N protein.
ABSTRACT
The outbreak of coronavirus disease (COVID-19) in China caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. It is currently no specific viral protein targeted therapeutics yet. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein is yet to be clear. Herein, we have determined the 2.7 [A] crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although overall structure is similar with other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the {beta}-sheet core. Complemented by in vitro binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.
ABSTRACT
The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. Currently, there is no specific viral protein-targeted therapeutics. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein remains unclear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the -sheet core. Complemented by binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.
ABSTRACT
BACKGROUND: The effects of low-level laser biostimulation have been proved by various experimental studies and clinical application, which are manifested as tissue repairing, analgesia, antiinflammation, etc.OBJECTIVE: To observe the effects of He-Ne laser and low-level CO2 laser irradiation on fracture healing.DESIGN: A randomized controlled animal experiment. SETTING: Research Room of Laser Medicine, Chengde Medical College.MATERIALS: Forty-eight healthy male New Zealand rabbits, weighing 2.0-2.5 kg, were used.METHODS: The experiments were carried out in the Research Room of Laser Medicine, Chengde Medical College from 1998 to 2003. ①The 48 rabbits were induced into models of experimental fracture of the left radius, and then they were divided into three groups with 16 rabbits in each group: control group, He-Ne laser irradiation group and CO2 laser irradiation group. The fracture areas of the animals in the He-Ne and CO2 laser irradiation groups were respectively irradiated with 28 mW/cm2 He-Ne laser and 150 mW/cm2 CO2 laser for 10 minutes, once a day. ② The animals were killed on the 15th and 35th days after taking roentgenogram respectively. At 15 days, the collagen and calcium contents in callus were detected. At 35 days, the biomechanic anti-torsion strength was examined.MAIN OUTCOME MEASURES: ①Results of roentgenogram in each group; ② Collagen and calcium contents in callus; ③ Results of biomechanic anti-torsion strength.RESULTS: Totally 45 rabbits were involved in the analysis of results. ① On the 15th and day after fracture, the roentgenogram, collagen and calcium contents in callus in the He-Ne and CO2 laser irradiation groups were better than those in the control group, and the collagen and calcium contents in callus were higher in the CO2 laser irradiation group than in the He-Ne laser irradiation group [(341.9±30.1) vs (302.1±28.7) mg/g; (197.1±19.7)vs (156.5±17.6) mg/g, P＜ 0.05]. ②On the 35th days after fracture, the biomechanic anti-torsion functions in the He-Ne and CO2 laser irradiation groups were superior to that in the control group, and there were no significant difference between the two laser irradiation groups. ③ The results of roentgenogram in the He-Ne and CO2 laser irradiation groups were better than that in the control group both on the 15th and 35th days after fracture, and there was no significant difference between the two irradiation groups.CONCLUSION: Both CO2 laser and He-Ne laser irradiations can accelerate the process of fracture healing, and the curative effect of CO2 laser is better than that of He-Ne laser on the 15th day after fracture, but there is no significant difference clinically between the CO2 laser and the He-Ne laser irradiations on the 35th day after fracture.
