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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. © 2024. The Author(s).


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. Aptamers targeting SARS-CoV-2 nucleocapsid protein exhibit potential anti pan-coronavirus activity. Signal transduction and targeted therapy. 2024 Feb 14;9(1):40

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PMID: 38355661

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