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Repurposing carrimycin as an antiviral agent against human coronaviruses,including the currently pandemic SARS-CoV-2

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Acta Pharmaceutica Sinica B 2021年第9期11卷 2850-2858页

作者： Haiyan Yan Jing Sun Kun Wang Huiqiang Wang Shuo Wu Linlin Bao Weiqing He Dong Wang Airu Zhu Tian Zhang Rongmei Gao Biao Dong Jianrui Li Lu Yang Ming Zhong Qi Lv Feifei Qin Zhen Zhuang Xiaofang Huang Xinyi Yang Yuhuan Li Yongsheng Che Jiandong Jiang Sciences and Peking Union Medical College Beijing 100050China state key laboratory of respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510182China Institute of Medicinal Biotechnology Chinese Academy of Medical ScienceBeijing 100050China key laboratory of Human Disease Comparative Medicine Chinese Ministry of HealthBeijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China School of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityBenxi 117004China

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic *** effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus *** report herein that a macrolide antibiotic,carrimycin,potently inhibited the cytopathic effects(CPE)and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229 E,OC43,and ***-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus *** support of this notion,metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral *** studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.

关键词： Coronavirus SARS-CoV-2 HCoV-229E HCoV-OC43 COVID-19 Carrimycin

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Comparison Between Threshold Method and Artificial Intelligence Approaches for Early Warning of respiratory Infectious Diseases-Weifang City,Shandong Province,China,2020-2023

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China CDC weekly 2024年第26期6卷 635-641,I0010,I0011页

作者： Ting Zhang Liuyang Yang Ziliang Fan Xuancheng Hu Jiao Yang Yan Luo Dazhu Huo Xuya Yu Ling Xin Xuan Han Jie Shan Zhongjie Li Weizhong Yang School of Population Medicine and Public health Chinese Academy of Medical Sciences(CAMS)&Peking Union Medical College(PUMC)BeijingChina state key laboratory of respiratory health and multimorbidity BeijingChina key laboratory of Pathogen Infection Prevention and Control(Peking Union Medical College) Ministry of EducationBeijingChina The Third Affiliated Hospital of Kunming Medical University Yunnan Cancer HospitalKunming CityYunnan ProvinceChina School of Data Science Fudan UniversityShanghaiChina Weifang Center for Disease Control and Prevention Weifang CityShandong ProvinceChina School of health Policy and Management Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

Introduction:respiratory infectious diseases,such as influenza and coronavirus disease 2019(COVID-19),present significant global public health *** emergence of artificial intelligence(AI)and big data offers opportunities to improve traditional disease surveillance and early warning ***:The study analyzed data from January 2020 to May 2023,comprising influenza-like illness(ILI)statistics,Baidu index,and clinical data from *** methodologies were evaluated:the adaptive dynamic threshold method(ADTM)for dynamic threshold adjustments,the machine learning supervised method(MLSM),and the machine learning unsupervised method(MLUM)utilizing anomaly *** comparison focused on sensitivity,specificity,timeliness,and warning ***:ADTM issued 37 warnings with a sensitivity of 71%and a specificity of 85%.MLSM generated 35 warnings,with a sensitivity of 82%and a specificity of 87%.MLUM produced 63 warnings with a sensitivity of 100%and specificity of 80%.The initial warnings from ADTM and MLUM preceded those from MLSM by five *** Kappa coefficient indicated moderate agreement between the methods,with values ranging from 0.52 to 0.62(Phealth preparedness and response,alongside acknowledging limitations and the need for broader validation.

关键词： specificity integrating utilizing

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Safety, immunogenicity and protective effectiveness of heterologous boost with a recombinant COVID-19 vaccine (Sf9 cells) in adult recipients of inactivated vaccines

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1165-1173页

作者： Wenxin Luo Jiadi Gan Zhu Luo Shuangqing Li Zhoufeng Wang Jiaxuan Wu Huohuo Zhang Jinghong Xian Ruixin Cheng Xiumei Tang Yi Liu Ling Yang Qianqian Mou Xue Zhang Yi Chen Weiwen Wang Yantong Wang Lin Bai Xuan Wei Rui Zhang Lan Yang Yaxin Chen Li Yang Yalun Li Dan Liu Weimin Li Lei Chen Department of Pulmonary and Critical Care Medicine West China HospitalSichuan UniversityChengduChina Institute of respiratory health Frontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengduChina Precision Medicine Center Precision Medicine Key Laboratory of Sichuan ProvinceWest China HospitalSichuan UniversityChengduChina state key laboratory of respiratory health and multimorbidity West China HospitalChengduChina Institute of respiratory health and multimorbidity West China HospitalSichuan UniversityChengduChina Clinical Trial Center West China HospitalSichuan UniversityChengduChina General Practice Medical Center West China HospitalSichuan UniversityChengduChina Fangcao Community health Service Center of Chengdu High-tech Zone ChengduChina The Research Units of West China Chinese Academy of Medical SciencesWest China HospitalChengduChina West China School of Nursing Sichuan UniversityChengduChina Department of Infection Control West China HospitalSichuan UniversityChengduChina Department of Pathology West China HospitalSichuan UniversityChengduChina Department of respiratory and Critical Care Medicine the First Affiliated Hospital of Chongqing Medical UniversityChongqingChina Department of Neurology West China HospitalSichuan UniversityChengduChina

Vaccines have proven effective in protecting populations against COVID-19,including the recombinant COVID-19 vaccine(Sf9 cells),the first approved recombinant protein vaccine in *** this positive-controlled trial with 85 adult participants(Sf9 cells group:n=44;CoronaVac group:n=41),we evaluated the safety,immunogenicity,and protective effectiveness of a heterologous boost with the Sf9 cells vaccine in adults who had been vaccinated with the inactivated vaccine,and found a post-booster adverse events rate of 20.45%in the Sf9 cells group and 31.71%in the CoronaVac group(p=0.279),within 28 days after booster *** group reported any severe adverse *** the Sf9 cells vaccine booster,the geometric mean titer(GMT)of binding antibodies to the receptor-binding domain of prototype SARS-CoV-2 on day 28 post-booster was significantly higher than that induced by the CoronaVac vaccine booster(100,683.37 vs.9,451.69,p<0.001).In the Sf9 cells group,GMTs of neutralizing antibodies against pseudo SARS-CoV-2 viruses(prototype and diverse variants of concern[VOCs])increased by 22.23–75.93 folds from baseline to day 28 post-booster,while the CoronaVac group showed increases of only 3.29–10.70 ***,neutralizing antibodies against live SARS-CoV-2 viruses(prototype and diverse VOCs)increased by 68.18–192.67 folds on day 14 post-booster compared with the baseline level,significantly greater than the CoronaVac group(19.67–37.67 folds).A more robust Th1 cellular response was observed with the Sf9 cells booster on day 14 post-booster(mean IFN-γ+spot-forming cells per 2×105 peripheral blood mononuclear cells:26.66 vs.13.59).Protective effectiveness against symptomatic COVID-19 was approximately twice as high in the Sf9 cells group compared to the CoronaVac group(68.18%vs.36.59%,p=0.004).Our study findings support the high protective effectiveness of heterologous boosting with the recombinant COVID-19 vaccine(Sf9 cells)against symptomatic COVID-19 of dive

关键词： protective vaccine boost

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Combinational benefit of antihistamines and remdesivir for reducing SARS-CoV-2 replication and alleviating inflammation-induced lung injury in mice

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Zoological Research 2022年第3期43卷 457-468页

作者： Meng-Li Wu Feng-Liang Liu Jing Sun Xin Li Jian-Ru Qin Qi-Hong Yan Xia Jin Xin-Wen Chen Yong-Tang Zheng Jin-Cun Zhao Jian-Hua Wang College of Life Science Henan Normal UniversityXinxiangHenan 453007China Guangzhou Institutes of Biomedicine and health Chinese Academy of SciencesGuangzhouGuangdong 510530China key laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China state key laboratory of respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthFirst Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510182China University of Chinese Academy of Sciences Beijing 100049China

COVID-19 is an immune-mediated inflammatory disease caused by SARS-CoV-2 infection,the combination of anti-inflammatory and antiviral therapy is predicted to provide clinical *** recently demonstrated that mast cells(MCs)are an essential mediator of SARS-CoV-2-initiated *** also showed that spike protein-induced MC degranulation initiates alveolar epithelial inflammation for barrier disruption and suggested an off-label use of antihistamines as MC stabilizers to block degranulation and consequently suppress inflammation and prevent lung *** this study,we emphasized the essential role of MCs in SARS-CoV-2-induced lung lesions in vivo,and demonstrated the benefits of co-administration of antihistamines and antiviral drug remdesivir in SARS-CoV-2-infected ***,SARSCoV-2 spike protein-induced MC degranulation resulted in alveolar-capillary injury,while pretreatment of pulmonary microvascular endothelial cells with antihistamines prevented adhesion junction disruption;predictably,the combination of antiviral drug remdesivir with the antihistamine loratadine,a histamine receptor 1(HR1)antagonist,dampened viral replication and inflammation,thereby greatly reducing lung *** findings emphasize the crucial role of MCs in SARS-CoV-2-induced inflammation and lung injury and provide a feasible combination antiviral and anti-inflammatory therapy for COVID-19 treatment.

关键词： SARS-CoV-2 Mast cell Remdesivir Antihistamine Combinational therapy

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Human adenovirus(HAdV)infection in children with acute respiratory tract infections in Guangzhou,China,2010–2021:a molecular epidemiology study

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World Journal of Pediatrics 2022年第8期18卷 545-552页

作者： Yi Chen Tao Lin Chang‑Bing Wang Wan‑Li Liang Guang‑Wan Lian Mark Zanin Sook‑San Wong Xin‑Gui Tian Jia‑Yu Zhong Ying‑Ying Zhang Jia‑Hui Xie Ling‑Ling Zheng Fei‑Yan Chen Run Dang Ming‑Qi Zhao Yi‑Yu Yang Rong Zhou Bing Zhu Center laboratory Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou 510120China state key laboratory of respiratory Diseases Guangzhou Institute of Respiratory HealthGuangzhou Medical UniversityGuangzhouChina Intensive Care Unit Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou 510120China Guangzhou Medical University Guangzhou 510120China

Background Human adenovirus(HAdV)infection can cause a variety of *** is a major pathogen of pediatric acute respiratory tract infections(ARIs)and can be life-threatening in younger *** described the epidemiology and subtypes shifting of HAdV among children with ARI in Guangzhou,*** We conducted a retrospective study of 161,079 children diagnosed with acute respiratory illness at the Guangzhou Women and Children’s Medical Center between 2010 and *** specimens were detected by real-time PCR and the hexon gene was used for phylogenetic *** Before the COVID-19 outbreak in Guangzhou,the annual frequency of adenovirus infection detected during this period ranged from 3.92%to 13.58%,with an epidemic peak every four to fve *** demonstrated a clear seasonal distribution,with the lowest positivity in March and peaking during summer(July or August)every year.A signifcant increase in HAdV cases was recorded for 2018 and 2019,which coincided with a shift in the dominant HAdV subtype from HAdV-3 to *** latter was associated with a more severe disease compared to *** average mortality proportion for children infected with HAdV from 2016 to 2019 was 0.38%but increased to 20%in severe *** COVID-19 emerged,HAdV cases dropped to 2.68%,suggesting that non-pharmaceutical interventions probably reduced the transmission of HAdV in the *** Our study provides the foundation for the understanding of the epidemiology of HAdV and its associated risks in children in Southern China.

关键词： Acute respiratory tract infection Children Human adenovirus Severe acute hepatitis Southern China

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SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular Cl^(-)concentration

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1745-1759页

作者： Jian-Bang Xu Wei-Jie Guan Yi-Lin Zhang Zhuo-Er Qiu Lei Chen Xiao-Chun Hou Junqing Yue Yu-Yun Zhou Jie Sheng Lei Zhao Yun-Xin Zhu Jing Sun Jincun Zhao Wen-Liang Zhou Nan-Shan Zhong state key laboratory of respiratory Disease National Clinical Research Center for Respiratory DiseaseNational Center for Respiratory MedicineDepartment of Respiratory and Critical Care MedicineGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Department of Thoracic Surgery Guangzhou Institute for Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Guangzhou National laboratory GuangzhouP.R.China School of Life Sciences Sun Yat-sen UniversityGuangzhouP.R.China Guangdong Provincial key laboratory of Pharmaceutical Functional Genes School of Life SciencesSun Yat-sen UniversityGuangzhouP.R.China Department of Physiology School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhouP.R.China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection disrupts the epithelial barrier and triggers airway *** envelope(E)protein,a core virulence structural component of coronaviruses,may play a role in this *** could interfere with transepithelial Cl^(-)transport via impairment of the cystic fibrosis transmembrane conductance regulator(CFTR),which modulates nuclear factor kB(NF-kB)***,the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function,Cl^(-)transport and the robust inflammatory response remain to be ***,we have demonstrated that E protein down-regulated the expression of tight junctional proteins,leading to the disruption of the airway epithelial *** addition,E protein triggered the activation of Toll-like receptor(TLR)2/4 and downstream c-Jun N-terminal kinase(JNK)signaling,resulting in an increased intracellular Cl^(-)concentration([Cl^(-)]_(i))via up-regulating phosphodiesterase 4D(PDE4D)expression in airway epithelial *** elevated[Cl^(-)]_(i);contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1(SGK1).Moreover,blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E ***,these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.

关键词： airway inflammation elevated

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Heparin-binding protein as a predictor of mortality in patients with diabetes mellitus and community-acquired pneumonia in intensive care unit:a propensity score matched study

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World Journal of Emergency Medicine 2024年第4期15卷 263-272页

作者： Yuhan Sun Baoqing Sun Zhigang Ren Mingshan Xue Changju Zhu Qi Liu Translational Medicine Center Department of Emergency Medicinethe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China state key laboratory of respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China Department of Infectious Disease the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Medical key laboratory of Emergency and Trauma Research Department of Emergency Medicinethe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

BACKGROUND:Patients with diabetes mellitus(DM)are vulnerable to community-acquired pneumonia(CAP),which have a high mortality *** aimed to investigate the value of heparin-binding protein(HBP)as a prognostic marker of mortality in patients with DM and ***:This retrospective study included CAP patients who were tested for HBP at intensive care unit(ICU)admission from January 2019 to April *** were allocated to the DM or non-DM group and paired with propensity score *** characteristics and clinical outcomes up to 90 days were *** primary outcome was the 10-day *** operating characteristic(ROC)curves,Kaplan-Meier analysis,and Cox regression were used for statistical ***:Among 152 enrolled patients,60 pairs were successfully *** was no significant difference in 10-day mortality,while more patients in the DM group died within 28 d(P=0.024)and 90 d(P=0.008).In the DM group,HBP levels at ICU admission were higher in 10-day non-survivors than in 10-day survivors(median 182.21[IQR:55.43-300]ng/ml *** 66.40[IQR:34.13-107.85]ng/mL,P=0.019),and HBP levels could predict the 10-day mortality with an area under the ROC curve of *** cut-off value,sensitivity,and specificity were 160.6 ng/mL,66.7%,and 90.2%,*** Cox regression analysis indicated that HBP was an independent prognostic factor for 10-day(HR 7.196,95%CI:1.596-32.455,P=0.01),28-day(HR 4.381,95%CI:1.449-13.245,P=0.009),and 90-day mortality(HR 4.581,95%CI:1.637-12.819,P=0.004)in patients with ***:Plasma HBP at ICU admission was associated with the 10-day,28-day,and 90-day mortality,and might be a prognostic factor in patients with DM and CAP.

关键词： Community-acquired pneumonia Diabetes mellitus Heparin-binding protein Propensity score match

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DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1925-1951页

作者： Rui-Xue Huang Ping-Kun Zhou Department of Occupational and Environmental health Xiangya School of Public HealthCentral South University410078 ChangshaPeople’s Republic of China Department of Radiation Biology Beijing Key Laboratory for RadiobiologyBeijing Institute of Radiation MedicineAMMS100850 BeijingPeople’s Republic of China Institute for Chemical Carcinogenesis State Key Laboratory of RespiratoryGuangzhou Medical University511436 GuangzhouPeople’s Republic of China

Radiotherapy is one of the most common countermeasures for treating a wide range of ***,the radioresistance of cancer cells is still a major limitation for radiotherapy *** are continuously ongoing to explore sensitizing targets and develop radiosensitizers for improving the outcomes of *** double-strand breaks are the most lethal lesions induced by ionizing radiation and can trigger a series of cellular DNA damage responses(DDRs),including those helping cells recover from radiation injuries,such as the activation of DNA damage sensing and early transduction pathways,cell cycle arrest,and DNA ***,these protective DDRs confer tumor *** DDR signaling pathways has become an attractive strategy for overcoming tumor radioresistance,and some important advances and breakthroughs have already been achieved in recent *** the basis of comprehensively reviewing the DDR signal pathways,we provide an update on the novel and promising druggable targets emerging from DDR pathways that can be exploited for *** further discuss recent advances identified from preclinical studies,current clinical trials,and clinical application of chemical inhibitors targeting key DDR proteins,including DNA-PKcs(DNA-dependent protein kinase,catalytic subunit),ATM/ATR(ataxia–telangiectasia mutated and Rad3-related),the MRN(MRE11-RAD50-NBS1)complex,the PARP(poly[ADP-ribose]polymerase)family,MDC1,Wee1,LIG4(ligase IV),CDK1,BRCA1(BRCA1 C terminal),CHK1,and HIF-1(hypoxia-inducible factor-1).Challenges for ionizing radiation-induced signal transduction and targeted therapy are also discussed based on recent achievements in the biological field of radiotherapy.

关键词： damage radiotherapy injuries

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Variant PRC1 subunit RYBP/YAF2 forms condensate with RING1B and promotes H2AK119ub deposition

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Science China(Life Sciences) 2024年第9期67卷 2036-2038页

作者： Yanjiang Liu Gongcheng Hu Shengxiong Yang Chenghong Yan Juehan Wang Guangjin Pan Hongjie Yao state key laboratory of respiratory Disease Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou510530China Department of Basic Research Guangzhou National LaboratoryGuangzhou 510005China CAS key laboratory of Regenerative Biology Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China University of Chinese Academy of Sciences Beijing 100049China

Dear Editor,Polycomb group(Pc G)proteins represent important roles in repressing gene expression throughout *** Polycomb repressive complexes(PRCs)have been subdivided into two central protein complexes,PRC1 and ***1 catalyzes H2AK119ub and PRC2catalyzes H3K27me1/2/3(Fursova et al.,2019).PRC1 is further categorized as CBX-containing canonical PRC1(c PRC1)and RYBP/YAF2-containing variant PRC1(v PRC1)(Blackledge and Klose,2021).

关键词： PRC1 RING1 RYBP

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Biomedical and Environmental Sciences 2014年第7期27卷 495-505页

作者： SUN Bao Qing CHEN De Hui ZHENG Pei Yan HUANG Hui Min LUO Wen Ting ZENG Guang Qiao ZHANG Xiao Wen state key laboratory of respiratory Disease National Clinical Center for Respiratory DiseasesGuangzhou Institute of Respiratory DiseasesFirst Affiliated HospitalGuangzhou Medical University Department of Pediatrics First Affiliated HospitalGuangzhou Medical University Department of Otorhinolaryngology-Head & Neck Surgery First Affiliated HospitalGuangzhou Medical University

Objective To investigate the serum total IgE （tlgE） and specific IgE （slgE） to common allergens among allergic patients in Guangzhou, China. Methods 7 085 patients were examined for tlgE and slgE to 15 allergens, based on the protocols of reversed enzyme allergosorbent test and the sandwich enzyme-linked immunosorbent assay. Results 3 758 （53.04%） patients tested positive for tlgE, and 4 640 （65.49%） for slgE. Der pteronyssinus, Derfarinae, eggs, and cow＇s milk were the most common allergens leading to higher positive rates of slgE responses. Several peaks of sensitization were： Der pteronyssinus, Derfarinae, and Blomia tropicalis at age 10-12; cow＇s milk at age below 3; eggs at age 4-6. The mean level and positive rate of tlgE tended to increase in subjects sensitized to more allergens. Sensitization to Der pteronyssinus （OR, 1.6; P〈O.05）, Der farinae （OR, 1.5; P〈O.05）, Blomia tropicalis （OR, 1.4; P〈O.05）, Blattella germanica （OR, 1.5; P〈O.05）, cow＇s milk （OR, 1.3; P〈O.05）, and soy beans （OR, 2.0; P〈O.05） were independently correlated with allergy-related conditions in preliminary diagnosis. Conclusion The major allergens in Guangzhou include Derpteronyssinus, Derfarinae, cow＇s milk, and eggs. Sensitization to these allergens appears to be predictors of allergy-related disorder.

关键词： Allergy Allergen Symptoms Serum IgE

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