关键词： 新型冠状病毒   刺突蛋白   先天性免疫  

摘要： 由新型冠状病毒(Severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)引发的新型冠状病毒感染(Corona virus disease 2019,COVID-19),对全球公共卫生安全造成了巨大威胁。在病毒变异株不断出现和针对COVID-19安全有效的药物尚未上市的临床大背景下,深入探索病毒感染过程中关键的致病因素十分重要。先天免疫系统是机体抵御病毒入侵的第一道防线。基于大量的临床数据,研究人员发现严重紊乱的免疫应答反应是COVID-19患者死亡的主要原因之一。刺突蛋白(Spike protein,S蛋白)作为病毒关键的抗原蛋白,已被证明在病毒入侵过程和机体免疫应答失调阶段中发挥重要作用。本文综述了当前有关S蛋白与先天免疫系统相互作用的进展,以期为确定临床药物靶点和改善公共卫生防治策略提供帮助。

关键词： Branch retinal vein occlusion   AZD1222   ChAdOx1 nCoV-19   COVID-19 vaccine astraZeneca   vaxzevria   covishield   vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)  

摘要： Purpose To present a case of branch retinal vein occlusion (BRVO) following ChAdOx1 nCoV-19 (Oxford-AstraZeneca) Vaccine. Methods: Case report. Results: A 60-year old otherwise healthy Caucasian male, presented to the ophthalmology emergency clinic complaining of sudden, painless vision loss in his right eye of 24 h" duration. The patient had received Vaxveria seven days prior. The clinical and fundus examination of the right eye established the diagnosis of BRVO. Conclusion: The present case descibes the occurrence of BRVO soon after the vaccination with the Oxford-AstraZeneca vaccine. The close temporal relationship between the BRVO incidence and the vaccination is reinforced by the lack of othe subjective cause to justify the episode.

关键词： SARS-CoV-2   Adenovirus type 5-vectored vaccine   Inactivated vaccine   Heterologous immunisation   Elderly  

摘要： Background People over 60 have been found to develop less protection after two doses of inactivated COVID-19 vaccines than younger people. Heterologous immunisation could potentially induce more robust immune responses compared to homologous immunisation. We aimed to assess the immunogenicity and safety of a heterologous immunisation with an adenovirus type 5-vectored vaccine (Ad5-nCOV, Convidecia) among elderly who were primed with an inactivated vaccine (CoronaVac) *** We did a randomised, observer-blinded, non-inferiority trial in healthy adults aged 60 years and older in Lianshui County (Jiangsu, China) between August 26, 2021 and May 15, 2022. 199 eligible participants who had received two doses of CoronaVac in the past 3-6 months were randomised (1:1) to receive a third dose of Convidecia (group A, n = 99) or CoronaVac (group B, n = 100), while 100 participants primed with one dose of CoronaVac in the past 1-2 months were randomised equally to receive a second dose of Convidecia (group C, n = 50) or CoronaVac (group D, n = 50). Participants and investigators were masked to the vaccine received. Primary outcomes were the geometric mean titers (GMTs) of neutralising antibodies against live SARS-CoV-2 virus 14 days after boosting and 28-day adverse reactions. This study was registered with *** *** A heterologous third dose of Convidecia resulted in a 6.2-fold (GMTs: 286.4 vs 48.2), 6.3-fold (45.9 vs 7.3) and 7.5-fold (32.9 vs 4.4) increase in neutralising antibodies against SARS-CoV-2 wild-type, delta (B.1.617.2) and omicron (BA.1.1) 14 days post boosting, respectively, compared with the homologous boost. The heterologous booster with Convidecia induced significantly higher neutralsing activities, with up to 91% inhibition in binding of Spike to ACE2 for BA.4 and BA.5 variants, compared with 35% inhibition induced by three doses of CoronaVac. For participants primed with one dose of CoronaVac, a heterologous dose of

摘要： Background: There is limited data directly comparing the effectiveness of different COVID-19 ***: We compared rates of SARS-CoV-2 Omicron BA.1/2 infection during March to May 2022 in Australian adults who had received one of four COVID-19 vaccines in the last 14-63 days as either a primary course or a booster dose using Cox proportional hazards models adjusting for age and other ***: As a primary course, over 2318 person-years and 1033 infections, compared to recipients of BNT162b2 mRNA vaccine, adjusted hazard ratios for SARS-CoV-2 infection were 1.03 (95%CI 0.82-1.30), 1.19 (0.95-1.49), 1.70 (1.46-1.97) for respectively mRNA-1273, ChAdOx-1 nCov-19 and NVX-CoV2373. For the booster dose, over 154,984 person-years and 93,580 infections the respective adjusted hazard ratios compared to BNT162b2 mRNA vaccine were 1.02 (95%CI 1.00-1.04), 1.20 (1.10-1.32), 1.39 (1.20-1.60).Conclusions: Our findings suggest relatively higher effectiveness of ancestral strain mRNA vaccines against SARS-CoV-2 Omicron infection than viral vector and protein subunit vaccines and provide clinical confirmation of immunological data on differences in COVID-19 vaccine performance.

关键词： 新型冠状病毒   主蛋白酶   荧光偏振筛选模型   桑辛素   抑制作用  

摘要： 目的探讨桑辛素对新型冠状病毒主蛋白酶的抑制作用。方法利用软件AutoDock将桑辛素与主蛋白酶晶体结构6LU7的活性位点进行分子对接；而后利用主蛋白酶荧光偏振筛选模型检验桑辛素对于新型冠状病毒主蛋白酶的抑制活性。结果桑辛素与主蛋白酶活性位点具有较强的分子间相互作用，分子对接过程释放的自由能为-8.3kcal/mol；在药理活性测试中，桑辛素在400μmol/L、200μmol/L、100μmol/L、25μmol/L浓度对主蛋白酶的抑制率分别45%、34%、8%、1%。结论 实验表明，桑辛素具有一定的主蛋白酶抑制活性。与笔者既往报道的小分子黄酮类化合物相比，桑辛素对主蛋白酶的抑制活性明显增强，其原因可能为黄酮母核引入了脂溶性取代基进而增强了其与主蛋白酶活性位点处的结合能力相关，为黄酮母核类主蛋白酶抑制剂的结构优化提供参考。