Alterations of the oral microbiome in patients treated with the Invisalign system or with fixed appliances.

INTRODUCTION: Although the Invisalign system has been used widely in recent years, the influences of this treatment on the oral microbiome and whether or not this influence is different from that of fixed appliances is still unknown. In this study, we investigated the changes in the oral microbiome in patients treated with the Invisalign system or with fixed appliances. METHODS: Fifteen subjects were enrolled, comprising 5 fixed appliance patients, 5 Invisalign patient, and 5 healthy controls. Saliva samples were collected, and high-throughput pyrosequencing was performed based on the 16S rRNA gene. RESULTS: Both fixed and Invisalign orthodontic treatments resulted in dysbiosis of the oral microbiome. Firmicutes and TM7 at the phyla level and Neisseria at the genus level displayed statistically significant differences between the 2 orthodontic groups. The effect of these changes with microbiome on oral health was inconsistent. The inferred microbial function of the Invisalign group suggested this group was more predisposed to periodontal diseases. CONCLUSION: The influence of the Invisalign system on the oral microbiome was no better for oral health compared with fixed appliances. The convenience of maintaining oral hygiene rather than changes in the oral microbiome may be the underlying reason for the performance of the Invisalign system on oral health.

Identification and biochemical characterization of DC07090 as a novel potent small molecule inhibitor against human enterovirus 71 3C protease by structure-based virtual screening.

Hand, foot and mouth disease (HFMD) is a serious, highly contagious disease. HFMD caused by Enterovirus 71 (EV71), results in severe complications and even death. The pivotal role of EV71 3Cpro in the viral life cycle makes it an attractive target for drug discovery and development to treat HFMD. In this study, we identified novel EV71 3Cpro inhibitors by docking-based virtual screening. Totally 50 compounds were selected to test their inhibitory activity against EV71 3Cpro. The best inhibitor DC07090 exhibited the inhibition potency with an IC50 value of 21.72 ± 0.95 µM without apparent toxicity (CC50 > 200 µM). To explore structure-activity relationship of DC07090, 15 new derivatives were designed, synthesized and evaluated in vitro enzyme assay accordingly. Interestingly, four compounds showed inhibitory activities against EV71 3Cpro and only DC07090 inhibited EV71 replication with an EC50 value of 22.09 ± 1.07 µM. Enzyme inhibition kinetic experiments showed that the compound was a reversible and competitive inhibitor. The Ki value was determined to be 23.29 ± 12.08 µM. Further molecular docking, MD simulation and mutagenesis studies confirmed the binding mode of DC07090 and EV71 3Cpro. Besides, DC07090 could also inhibit coxsackievirus A16 (CVA16) replication with an EC50 value of 27.76 ± 0.88 µM. Therefore, DC07090 represents a new non-peptidyl small molecule inhibitor for further development of antiviral therapy against EV71 or other picornaviruses.