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 ORCID: orcid.org/0000-0001-6335-3346,Ge Yang,Yuanyu Huang ORCID: orcid.org/0000-0003-3935-7245 &…Yongxiang Zhao ORCID: orcid.org/0000-0003-2214-5887

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.

https://doi.org/10.1038/s41392-024-01748-w

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