Carnosine to Combat Novel Coronavirus (nCoV): Molecular Docking and Modeling to Cocrystallized Host Angiotensin-Converting Enzyme 2 (ACE2) and Viral Spike Protein

Aims: Angiotensin-converting enzyme 2 (ACE2) plays an important role in the entry of coronaviruses into host cells. The current paper described how carnosine, a naturally occurring supplement, can be an effective drug candidate for coronavirus disease (COVID-19) on the basis of molecular docking and modeling to host ACE2 cocrystallized with nCoV spike protein. Methods: First, the starting point was ACE2 inhibitors and their structure–activity relationship (SAR). Next, chemical similarity (or diversity) and PubMed searches made it possible to repurpose and assess approved or experimental drugs for COVID-19. Parallel, at all stages, the authors performed bioactivity scoring to assess potential repurposed inhibitors at ACE2. Finally, investigators performed molecular docking and modeling of the identified drug candidate to host ACE2 with nCoV spike protein. Results: Carnosine emerged as the best-known drug candidate to match ACE2 inhibitor structure. Preliminary docking was more optimal to ACE2 than the known typical angiotensin-converting enzyme 1 (ACE1) inhibitor (enalapril) and quite comparable to known or presumed ACE2 inhibitors. Viral spike protein elements binding to ACE2 were retained in the best carnosine pose in SwissDock at 1.75 Angstroms. Out of the three main areas of attachment expected to the protein–protein structure, carnosine bound with higher affinity to two compared to the known ACE2 active site. LibDock score was 92.40 for site 3, 90.88 for site 1, and inside the active site 85.49. Conclusion: Carnosine has promising inhibitory interactions with host ACE2 and nCoV spike protein and hence could offer a potential mitigating effect against the current COVID-19 pandemic.     

全科医生对社区糖尿病患者的防治

目的探讨和分析全科医生在社区糖尿病患者疾病防治中的效用。方法以2015年1月—2016年12月期间深圳市坪山新区人民医院碧岭社康中心管理的180例糖尿病患者为研究对象,并采用随机分组的方法分为观察组(n=90)和对照组(n=90),其中,观察组患者予以药物治疗,对照组患者予以非药物治疗,并观察和比较两组患者治疗前后的各种代谢指标。结果无论是在接受全科医生指导前还是指导后,观察组患者空腹血糖值和餐后2 h血糖值均明显低于对照组,且差异均具有统计学意义(P<0.05);观察组患者的糖化血红蛋白值、尿微量蛋白值、收缩压和舒张压值以及体质量指数明显低于对照组,且差异均具有统计学意义(P<0.05)。结论实施药物治疗的糖尿病患者的各项血糖及代谢指标均低于非药物治疗组的数值,全科医生在社区糖尿病患者的防治中发挥着一定的积极效用。