Aptamers targeting SARS-CoV-2 nucleocapsid protein exhibit potential anti pan-coronavirus activity

Yang, Minghui1; Li, Chunhui1; Ye, Guoguo2; Shen, Chenguang3; Shi, Huiping1; Zhong, Liping4; Tian, Yuxin1; Zhao, Mengyuan1; Wu, Pengfei1; Hussain, Abid1; Zhang, Tian1; Yang, Haiyin1; Yang, Jun1; Weng, Yuhua1; Liu, Xinyue1; Wang, Zhimin1; Gan, Lu4; Zhang, Qianyu4; Liu, Yingxia2; Yang, Ge5; Huang, Yuanyu1; Zhao, Yongxiang4

2024-02-14

10.1038/s41392-024-01748-w

SIGNAL TRANSDUCTION AND TARGETED THERAPY   影响因子和分区

2095-9907

2059-3635

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.

SCI

英语

其他

Natural Science Foundation of Guangxi Province (Guangxi Natural Science Foundation)["2021YFA1201000","2021YFC2302400","2023YFC2606004"] ; National Key Research & Development Program of China[AB20117001] ; Guangxi Science and Technology Development Program["82204263","32171394","32001008"] ; National Natural Science Foundation of China["3332022055","2022CX01013"] ; Fundamental Research Funds for the Central Universities[2022M720438] ; China Postdoctoral Science Foundation[20220484207] ; Beijing Nova Program (Interdisciplinary Cooperation Project) from Beijing Municipal Science & Technology Commission[XSQD-6120220072]

Biochemistry & Molecular Biology ; Cell Biology

Biochemistry & Molecular Biology ; Cell Biology

WOS:001162671200003

SPRINGERNATURE

Web of Science

1.Beijing Inst Technol, Adv Res Inst Multidisciplinary Sci, Sch Life Sci, Key Lab Mol Med & Biotherapy, Beijing 100081, Peoples R China
2.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Natl Clin Res Ctr Infect Dis, Affiliated Hosp 2, Shenzhen 518112, Peoples R China
3.Southern Med Univ, Sch Publ Hlth, Guangdong Prov Key Lab Trop Dis Res, Guangzhou 510515, Peoples R China
4.Guangxi Med Univ, Natl Ctr Int Res Biotargeting Theranost, Collaborat Innovat Ctr Targeting Tumor Diag & Ther, State Key Lab Targeting Oncol,Guangxi Key Lab Biot, Nanning 530021, Peoples R China
5.Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biotechnol, Beijing Key Lab Antimicrobial Agents, CAMS Key Lab Antiviral Drug Res, Beijing 100730, Peoples R China

Yang, Minghui,Li, Chunhui,Ye, Guoguo,et al. Aptamers targeting SARS-CoV-2 nucleocapsid protein exhibit potential anti pan-coronavirus activity[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2024,9(1).

Yang, Minghui.,Li, Chunhui.,Ye, Guoguo.,Shen, Chenguang.,Shi, Huiping.,...&Zhao, Yongxiang.(2024).Aptamers targeting SARS-CoV-2 nucleocapsid protein exhibit potential anti pan-coronavirus activity.SIGNAL TRANSDUCTION AND TARGETED THERAPY,9(1).

Yang, Minghui,et al."Aptamers targeting SARS-CoV-2 nucleocapsid protein exhibit potential anti pan-coronavirus activity".SIGNAL TRANSDUCTION AND TARGETED THERAPY 9.1(2024).