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Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation

Journal of Pharmaceutical Analysis 2024年第1期14卷 115-127页

作者： Yang Yi Wenzhe Li Kefang Liu Heng Xue Rong Yu Meng Zhang Yang-Oujie Bao Xinyuan Lai Jingjing Fan Yuxi Huang Jing Wang Xiaomeng Shi Junhua Li hongping wei Kuanhui Xiang Linjie Li Rong Zhang Xin Zhao Xue Qiao Hang Yang Min Ye State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing100191China Yunnan Baiyao International Medical Research Center Peking UniversityBeijing100191China CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing100101China CAS Key Laboratory of Special Pathogens and Biosafety Center for Biosafety Mega-ScienceWuhan Institute of VirologyChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing100049China Department of Microbiology and Infectious Disease Center School of Basic Medical SciencesPeking University Health Science CenterPeking UniversityBeijing100191China Hubei Jiangxia Laboratory Wuhan430000China Shenzhen Children's Hospital ShenzhenGuangdong518036China

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016μM.The mechanism was related to binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quantum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)pathways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

关键词： COVID-19 Inflammation Licorice-saponin A3 Receptor-binding domain(RBD) SARS-CoV-2

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ACE2-Targeting antibody suppresses SARS-CoY-2 Omicron and Delta variants

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Signal Transduction and Targeted Therapy 2022年第3期7卷 613-615页

作者： Jianxia Ou Yanan Zhang Yongmei Wang Zherui Zhang hongping wei Junping Yu Qi Wang Guifeng Wang Bo Zhang Chunhe Wang Biotheropeutics Discovery Research Center Shanghai Institute of Materia MedicoShanghaiChina School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjingChina Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhanChina University of Chinese Academy of Sciences BeijingChina

Dear Editor,The pandemic of COVID-19 continues worldwide with many variants arising,especially SARS-CoV-2 Delta(B.1.617.2)and Omicron(B.1.1.529)variants of concern(VOCs).According to WHO,Omicron has spread in almost a... 详细信息

关键词： Delta doubling variants

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Increased pathogenicity and aerosol transmission for one SARS-CoV-2 B.1.617.2 Delta variant over the wild-type strain in hamsters

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Virologica Sinica 2022年第6期37卷 796-803页

作者： Xinghai Zhang Shaohong Chen Zengguo Cao Yanfeng Yao Junping Yu Junhui Zhou Ge Gao Ping He Zhuo Dong Jie Zhong Jing Luo hongping wei Huajun Zhang State Key Laboratory of Virology Key Laboratory of Special Pathogens and BiosafetyWuhan Institute of VirologyChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing101409China Hubei International Travel Healthcare Center(Wuhan Customs Port Outpatient Department) Wuhan430040China

During the two-year pandemic of coronavirus disease 2019(COVID-19), its causative agent, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has been evolving. SARS-CoV-2 Delta, a variant of concern, has become the dominant circulating strain worldwide within just a few months. Here, we performed a comprehensive analysis of a new B.1.617.2 Delta strain(Delta630) compared with the early WIV04 strain(WIV04) in vitro and in vivo, in terms of replication, infectivity, pathogenicity, and transmission in hamsters. When inoculated intranasally, Delta630 led to more pronounced weight loss and more severe disease in hamsters. Moreover, 40%mortality occurred about one week after infection with 10^(4)PFU of Delta630, whereas no deaths occurred even after infection with 10^(5)PFU of WIV04 or other strains belonging to the Delta variant. Moreover, Delta630outgrew over WIV04 in the competitive aerosol transmission experiment. Taken together, the Delta630 strain showed increased replication ability, pathogenicity, and transmissibility over WIV04 in hamsters. To our knowledge, this is the first SARS-CoV-2 strain that causes death in a hamster model, which could be an asset for the efficacy evaluation of vaccines and antivirals against infections of SARS-CoV-2 Delta strains. The underlying molecular mechanisms of increased virulence and transmission await further analysis.

关键词： SARS-CoV-2 B.1.617.2 Delta variant Syrian hamsters Pathogenicity Transmission

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Molecular dissection of phage lysin PlySs2: integrity of the catalytic and cell wall binding domains is essential for its broad lytic activity

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Virologica Sinica 2015年第1期30卷 45-51页

作者： Yanling Huang Hang Yang Junping Yu hongping wei Key Laboratory of Special Pathogens and Biosafety Center for Emerging Infectious Diseases Wuhan Institute of Virology Chinese Academy of Sciences

The novel phage lysin PlySs2, is reported to be highly active against various bacteria, including staphylococci, streptococci and Listeria. However, the molecular mechanisms underlying its broad lytic spectrum remain to be established. In the present study, the lytic activity of the catalytic domain(CD, PlySc) and binding specificity of the cell wall binding domain(CBD, PlySb) of PlySs2 were examined. Our results showed that PlySc alone maintains very limited lytic activity. Enhanced green fluorescent protein(EGFP)-fused PlySb displayed high binding affinity to the streptococcal strains tested, including S.suis, S.dysgalactiae, and S.agalactiae, but not staphylococci, supporting its utility as a good CBD donor for streptococcal-targeted lysin engineering. EGFP-fused intact PlySs2 similarly displayed high affinity for streptococci, but not staphylococci. Notably, four truncated PlySb fragments showed no binding capacity. These findings collectively indicate that integrity of the PlySc and PlySb domains is an essential determinant of the broad lytic activity of PlySs2.

关键词： streptococci lysin cell wall binding domain catalytic domain bacterial resistance

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Schaftoside inhibits 3CL^(pro)and PL^(pro)of SARS-CoV-2 virus and regulates immune response and inflammation of host cells for the treatment of COVID-19

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Acta Pharmaceutica Sinica B 2022年第11期12卷 4154-4164页

作者： Yang Yi Meng Zhang Heng Xue Rong Yu Yang-Oujie Bao Yi Kuang Yue Chai Wen Ma Jing Wang Xiaomeng Shi Wenzhe Li wei Hong Junhua Li Elishiba Muturi hongping wei Joachim Wlodarz Szczepan Roszak Xue Qiao Hang Yang Min Ye State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China CAS Key Laboratory of Special Pathogens and Biosafety Center for Biosafety Mega-ScienceWuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China University of Chinese Academy of Sciences Bejing 100049China Faculty of Science and Technology University of SilesiaKatowice 40-007Poland Department of Phrysical and Quantum Chenmistry Faculty of ChemistryWroclaw University of Science and Technology Wroclaw 50-370Poland

It is an urgent demand worldwide to control the coronavirus disease 2019(COVID-19)pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The 3-chymotrypsin-like protease(3CL^(pro))and papain-like protease(PL^(pro))are key targets to discover SARS-CoV-2 inhibitors.After screening 12 Chinese herbal medicines and 125 compounds from licorice,we found that a popular natural product schaftoside inhibited 3CL^(pro)and PL^(pro)with IC_(50)values of 1.73±0.22 and 3.91±0.19μmol/L,respectively,and inhibited SARS CoV-2 virus in Vero E6 cells with EC_(50)of 11.83±3. 23μmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of3CLpro, and K157, E167 and A246 of PLpro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The antiinflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.

关键词： COVID-19 SARS-CoV-2 3-Chymotrypsin-like protease Papain-like protease Licorice Schaftoside Immune response Infammation

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Isolation and complete genome sequence of a novel virulent mycobacteriophage, CASbig

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Virologica Sinica 2015年第1期30卷 76-79页

作者： Tieshan Teng Junping Yu Hang Yang hongping wei Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of Virology Chinese Academy of Sciences University of Chinese Academy of Sciences

Dear Editor,Bacteriophages are powerful tools for investigating and manipulating their hosts(Fernandes et al.,2014).This holds particularly true for mycobacteriophages,which have facilitated the development of mycobac... 详细信息

关键词： powerful holds phage lysin CASbig similarity http Genome accession packaging

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鄂尔多斯盆地东部边界的构造学分析:以石楼北地区为例

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古地理学报 2024年第1期26卷 150-164页

作者：石婧何登发包洪平魏柳斌中国地质大学(北京)能源学院北京100083 中国石油长庆油田公司勘探开发研究院陕西西安710018

通常认为鄂尔多斯东部边界带由晋西挠褶带和离石断裂组成,但这一边界为残余边界,并非原始的沉积边界。文中以石楼北区域为例,过该区域构建了1条鄂尔多斯盆地东部盆-山尺度的区域地质大剖面,运用2D-Move软件进行构造演化的反演与正演模拟... 详细信息

通常认为鄂尔多斯东部边界带由晋西挠褶带和离石断裂组成,但这一边界为残余边界,并非原始的沉积边界。文中以石楼北区域为例,过该区域构建了1条鄂尔多斯盆地东部盆-山尺度的区域地质大剖面,运用2D-Move软件进行构造演化的反演与正演模拟,对其构造变形进行定量分析,并根据研究结果对鄂尔多斯盆地东部边界进行重新厘定。研究认为:(1)石楼北地区在加里东晚期受深部基底断裂活动影响,奥陶系膏盐岩层中形成盐滑脱褶皱,之后沉积石炭系—白垩系,至燕山期受到东西向的挤压应力,地层整体发生掀斜,最终在新生代吕梁隆起加速隆升,遭受差异风化剥蚀形成现今构造格局。(2)构建的区域地质大剖面现今长度为263.76 km,海拔最高可达2000 m,从加里东晚期到白垩纪地层缩短量为3.14 km,缩短率为1.18%,地层抬升高度为3.82 km。(3)根据地层、构造、演化特征对燕山运动期鄂尔多斯盆地的东部边界进行重新厘定,认为东部边界应向东延伸至吕梁隆起东侧。该成果可为鄂尔多斯盆地东缘范围、构造变形研究以及晋西挠褶带煤层气勘探开发提供参考与新思路。

关键词：鄂尔多斯盆地构造特征构造演化断层相关褶皱东部边界

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SARS-CoV-2/COVID-19 laboratory biosafety practices and current molecular diagnostic tools

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Journal of Biosafety and Biosecurity 2021年第2期3卷 131-140页

作者： Raphael Nyaruaba Caroline Mwaliko wei Hong Patrick Amoth hongping wei CAS Key Laboratory of Special Pathogens and Biosafety Centre for Biosafety Mega-ScienceWuhan Institute of VirologyChinese Academy of SciencesWuhanChina College of Life Sciences University of Chinese Academy of SciencesBeijingChina Sino-Africa Joint Research Center NairobiKenya CAS Key Laboratory of Molecular Virology&Immunology Institut Pasteur of ShanghaiChinese Academy of SciencesShanghaiChina Ministry of Health Government of KenyaNairobiKenya

The ongoing severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)/coronavirus disease 2019(COVID-19)pandemic has crippled several countries across the globe posing a serious global public health challenge.Despite the massive rollout of vaccines,molecular diagnosis remains the most important method for timely isolation,diagnosis,and control of COVID-19.Several molecular diagnostic tools have been developed since the beginning of the pandemic with some even gaining emergency use authorization from the United States(US)Food and Drug Administration for in vitro diagnosis of SARS-CoV-2.Herein,we discuss the working principles of some commonly used molecular diagnostic tools for SARS-CoV-2 including nucleic acid amplification tests,isothermal amplification tests,and rapid diagnostic tests.To ensure successful detection while minimizing the risk of cross-infection and misdiagnosis when using these diagnostic tools,laboratories should adhere to proper biosafety practices.Hence,we also present the common biosafety practices that may ensure the successful detection of SARS-CoV-2 from specimens while protecting laboratory workers and non-suspecting individuals from being infected.From this review article,it is clear that the SARS-CoV-2 pandemic has led to an increase in molecular diagnostic tools and the formation of new biosafety protocols that may be important for future and ongoing outbreaks.

关键词： Biosafety RDTs NAATs RT-PCR IATs COVID-19 SARS-CoV-2 Diagnosis

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Developing a bacteriophage cocktail for biocontrol of potato bacterial wilt

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Virologica Sinica 2017年第6期32卷 476-484页

作者： Cuihua wei Junli Liu Alice Nyarnbura Maina Francis B Mwaura Junping Yu Chenghui Yan Ruofang Zhang hongping wei Key Laboratory of Emerging Pathogens and Biosafety Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China University of Chinese Academy of Sciences Beijing 100039China Inner Mongolia Potato Engineering&Technology Research Center Inner Mongolia UniversityHohhot 010021China University of Nairobi Nairobi 00100Kenya Technical University of Kenya Nairobi 00200Kenya Sino-Africa Joint Research Center Nairobi 00200Kenya

Bacterial wilt is a devastating disease of potato and can cause an 80% production loss. To control wilt using bacteriophage therapy, we isolated and characterized twelve lytic bacteriophages from different water sources in Kenya and China. Based on the lytic curves of the phages with the pathogen Ralstonia solanacearum, one optimal bacteriophage cocktail, P1, containing six phage isolations was formulated and used for studying wilt prevention and treatment efficiency in potato plants growing in pots. The preliminary tests showed that the phage cocktail was very effective in preventing potato bacterial wilt by injection of the phages into the plants or decontamination of sterilized soil spiked with R. solanacearum. Eighty percent of potato plants could be protected from the bacterial wilt(caused by R. solanacearum reference strain GIM1.74 and field isolates), and the P1 cocktail could kill 98% of live bacteria spiked in the sterilized soil at one week after spraying.However, the treatment efficiencies of P1 depended on the timing of application of the phages, the susceptibility of the plants to the bacterial wilt, as well as the virulence of the bacteria infected,suggesting that it is important to apply the phage therapy as soon as possible once there are early signs of the bacterial wilt. These results provide the basis for the development of bacteriophagebased biocontrol of potato bacterial wilt as an alternative to the use of antibiotics.

关键词： Ralstonia solanacearum bacterial wilt potato bacteriophage therapy

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Enriched Opportunistic Pathogens Revealed by Metagenomic Sequencing Hint Potential Linkages between Pharyngeal Microbiota and COVID-19

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Virologica Sinica 2021年第5期36卷 924-933页

作者： Dongyan Xiong Caroline Muema Xiaoxu Zhang Xinming Pan Jin Xiong Hang Yang Junping Yu hongping wei CAS Key Laboratory of Special Pathogens and Biosafety Centre for Biosafety Mega-SciencesWuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China University of Chinese Academy of Sciences Beijing 100049China Jiangxia District Center for Disease Control and Prevention Wuhan 430200China

As a respiratory tract virus,SARS-CoV-2 infected people through contacting with the upper respiratory tract first.Previous studies indicated that microbiota could modulate immune response against pathogen infection.In the present study,we performed metagenomic sequencing of pharyngeal swabs from eleven patients with COVID-19 and eleven Non-COVID-19 patients who had similar symptoms such as fever and cough.Through metagenomic analysis of the above two groups and a healthy group from the public data,there are 6502 species identified in the samples.Specifically,the Pielou index indicated a lower evenness of the microbiota in the COVID-19 group than that in the Non-COVID-19 group.Combined with the linear discriminant analysis(LDA)and the generalized linear model,eighty-one bacterial species were found with increased abundance in the COVID-19 group,where 51 species were enriched more than 8 folds.The top three enriched genera were Streptococcus,Prevotella and Campylobacter containing some opportunistic pathogens.More interestingly,through experiments,we found that two Streptococcus strains,S.suis and S.agalactiae,could stimulate the expression of ACE2 of Vero cells in vitro,which may promote SARS-CoV-2 infection.Therefore,these enriched pathogens in the pharynxes of COVID-19 patients may involve in the virus-host interactions to affect SARS-CoV-2 infection and cause potential secondary bacterial infections through changing the expression of the viral receptor ACE2 and/or modulate the host’s immune system.

关键词： COVID-19 Metagenome sequencing ACE2 Streptococcus Prevotella Campylobacter

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