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

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 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

作者机构：School of Life ScienceAdvanced Research Institute of Multidisciplinary ScienceKey Laboratory of Molecular Medicine and BiotherapyBeijing Institute of TechnologyBeijing 100081China National Clinical Research Center for infectious diseaseShenzhen Third People’s HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhen 518112China Guangdong Provincial Key Laboratory of Tropical Disease ResearchSchool of Public HealthSouthern Medical UniversityGuangzhou 510515China State Key Laboratory of Targeting OncologyNational Center for International Research of Biotargeting TheranosticsGuangxi Key Laboratory of Biotargeting TheranosticsCollaborative Innovation Center for Targeting Tumor Diagnosis and TherapyGuangxi Medical UniversityNanning 530021China CAMS Key Laboratory of Antiviral Drug ResearchBeijing Key Laboratory of Antimicrobial AgentsInstitute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2024年第9卷第3期

页      面：1186-1198页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学] 

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 

主　　题：acute threat conclusion 

摘      要：Emerging and recurrent infectious diseases caused by human coronaviruses(HCoVs)continue to pose a significant threat to global public health *** light of this ongoing threat,the development of a broad-spectrum drug to combat HCoVs is an urgently ***,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 *** 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,*** 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.