Aptamers targeting SARS-CoV-2 nucleocapsid protein exhibit potential ant1ip1 an-coronavirus activity  

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作  者:Minghui Yang Chunhui Li Guoguo Ye Chenguang Shen Huiping Shi Liping Zhong Yuxin Tian Mengyuan Zhao Pengfei Wu Abid Hussain Tian Zhang Haiyin Yang Jun Yang Yuhua Weng Xinyue Liu Zhimin Wang Lu Gan Qianyu Zhang Yingxia Liu Ge Yang Yuanyu Huang Yongxiang Zhao 

机构地区:[1]School of Life Science,Advanced Research Institute of Multidisciplinary Science,Key Laboratory of Molecular Medicine and Biotherapy,Beijing Institute of Technology,Beijing 100081,China [2]National Clinical Research Center for infectious disease,Shenzhen Third People’s Hospital,Second Hospital Affiliated to Southern University of Science and Technology,Shenzhen 518112,China [3]Guangdong Provincial Key Laboratory of Tropical Disease Research,School of Public Health,Southern Medical University,Guangzhou 510515,China [4]State Key Laboratory of Targeting Oncology,National Center for International Research of Biotargeting Theranostics,Guangxi Key Laboratory of Biotargeting Theranostics,Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy,Guangxi Medical University,Nanning 530021,China [5]CAMS Key Laboratory of Antiviral Drug Research,Beijing Key Laboratory of Antimicrobial Agents,Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China

出  处:《Signal Transduction and Targeted Therapy》2024年第3期1186-1198,共13页信号转导与靶向治疗(英文)

基  金:supported by the National Key Research&Development Program of China(2021YFA1201000,2021YFC2302400,2023YFC2606004);the Guangxi Science and Technology Development Program(AB20117001);the National Natural Science Foundation of China(82204263,32171394,32001008);the Fundamental Research Funds for the Central Universities(3332022055,2022CX01013);the China Postdoctoral Science Foundation(2022M720438);the Beijing Nova Program(Interdisciplinary Cooperation Project)from Beijing Municipal Science&Technology Commission(20220484207);We knowledge the Beijing Institute of Technology Research Fund Program for Young Scholars(XSQD-6120220072);We thank the Biological and Medical Engineering Core Facilities,and Analysis&Testing Center,Beijing Institute of Technology for supporting experimental equipment,and staffs for valuable help with technical support.

摘  要:Emerging and recurrent infectious diseases caused by human coronaviruses(HCoVs)continue to pose a significant threat to global public health security.In light of this ongoing threat,the development of a broad-spectrum drug to combat HCoVs is an urgently priority.Herein,we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment(SELEX).These aptamers have nanomolar affinity with the nucleocapsid protein(NP)of Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and also show excellent binding efficiency to the N proteins of both SARS,MERS,HCoV-OC43 and-NL63 with affinity KD values of 1.31 to 135.36 nM.Such aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant(BA.5)with EC50 values at 2.00 nM and 41.08 nM,respectively.The protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs(−229E and-HKU1).In conclusion,we have identified six aptamers with a high pan-coronavirus antiviral activity,which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.

关 键 词:acute THREAT CONCLUSION 

分 类 号:R373[医药卫生—病原生物学]

 

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