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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