SARS-Coronavirus-2 Nsp13 Possesses NTPase and RNA Helicase Activities That Can Be Inhibited by Bismuth Salts

Ting Shu; Muhan Huang; Di Wu; Yujie Ren; Xueyi Zhang; Yang Han; Jingfang Mu; Ruibing Wang; Yang Qiu; Ding-Yu Zhang; Xi Zhou

doi:10.1007/s12250-020-00242-1

June 2020

Ting Shu, Muhan Huang, Di Wu, Yujie Ren, Xueyi Zhang, Yang Han, Jingfang Mu, Ruibing Wang, Yang Qiu, Ding-Yu Zhang and Xi Zhou. SARS-Coronavirus-2 Nsp13 Possesses NTPase and RNA Helicase Activities That Can Be Inhibited by Bismuth Salts[J]. Virologica Sinica, 2020, 35(3): 321-329. doi: 10.1007/s12250-020-00242-1

Citation: Ting Shu, Muhan Huang, Di Wu, Yujie Ren, Xueyi Zhang, Yang Han, Jingfang Mu, Ruibing Wang, Yang Qiu, Ding-Yu Zhang, Xi Zhou. SARS-Coronavirus-2 Nsp13 Possesses NTPase and RNA Helicase Activities That Can Be Inhibited by Bismuth Salts .VIROLOGICA SINICA, 2020, 35(3) : 321-329. http://dx.doi.org/10.1007/s12250-020-00242-1

新型冠状病毒非结构蛋白nsp13具有NTPase活性和RNA解旋酶活性且该活性能被含铋复合物抑制

舒婷 ^1,2 ,
黄霂晗 ² ,
吴迪 ² ,
任玉洁 ^2,3 ,
张雪逸 ² ,
韩阳 ^1,2 ,
穆敬芳 ² ,
王瑞兵 ⁴ ,
邱洋 ^1,2,5 ,
张定宇 ^1,, ,
周溪 ^1,2,5,,

cstr: 32224.14.s12250-020-00242-1

1.
武汉市金银潭医院，转化医学中心

通讯作者： 张定宇, zhangdy63@hotmail.com, ORCID: http://orcid.org/0000-0002-9277-5705
; 周溪, zhouxi@wh.iov.cn, ORCID: http://orcid.org/0000-0002-3846-5079
收稿日期： 2020-05-07
录用日期： 2020-05-19
出版日期： 2020-06-04

摘要

SARS-coronavirus-2（SARS-CoV-2）是冠状病毒科（Coronaviridae）中一种正链RNA病毒。对于RNA病毒来说，病毒编码的RNA解旋酶通过促进病毒RNA的正确折叠和复制，在病毒的生命周期中发挥着重要作用。在本研究中，我们发现SARS-CoV-2编码的非结构蛋白nsp13具有核苷三磷酸水解酶（NTPase）和RNA解旋酶活性，nsp13可以水解所有类型的NTPs，并以依赖NTP的方式解旋双链RNA。此外，我们发现某些含铋复合物能以剂量依赖的方式有效抑制SARS-CoV-2 nsp13的NTPase和RNA解旋活性。综上，我们的研究证明了SARS-CoV-2 nsp13具有NTPase和解旋酶活性，其在SARS-CoV-2的复制中起重要作用，并可能作为抗病毒药物的潜在靶点。
- 新型冠状病毒
- , 非结构蛋白nsp13
- , NTPase
- , 解旋酶
- , 抗病毒药物

SARS-Coronavirus-2 Nsp13 Possesses NTPase and RNA Helicase Activities That Can Be Inhibited by Bismuth Salts

Ting Shu ^1,2 ,
Muhan Huang ² ,
Di Wu ² ,
Yujie Ren ^2,3 ,
Xueyi Zhang ² ,
Yang Han ^1,2 ,
Jingfang Mu ² ,
Ruibing Wang ⁴ ,
Yang Qiu ^1,2,5 ,
Ding-Yu Zhang ^1,, ,
Xi Zhou ^1,2,5,,

1.
Center for Translational Medicine, Wuhan Jinyintan Hospital, Wuhan 430023, China
2.
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
3.
Center for Precision Translational Medicine of Wuhan Institute of Virology and Guangzhou Women and Children's Medical Center, Guangzhou Women and Children's Medical Center, Guangzhou 510120, China
4.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR 999078, China
5.
University of Chinese Academy of Sciences, Beijing 100049, China

Corresponding author: Ding-Yu Zhang, zhangdy63@hotmail.com Xi Zhou, zhouxi@wh.iov.cn
ORCID: http://orcid.org/0000-0002-9277-5705; http://orcid.org/0000-0002-3846-5079
Received Date: 07 May 2020
Accepted Date: 19 May 2020
Published Date: 04 June 2020

Abstract

The ongoing outbreak of Coronavirus Disease 2019 (COVID-19) has become a global public health emergency. SARS-coronavirus-2 (SARS-CoV-2), the causative pathogen of COVID-19, is a positive-sense single-stranded RNA virus belonging to the family Coronaviridae. For RNA viruses, virus-encoded RNA helicases have long been recognized to play pivotal roles during viral life cycles by facilitating the correct folding and replication of viral RNAs. Here, our studies show that SARS-CoV-2-encoded nonstructural protein 13 (nsp13) possesses the nucleoside triphosphate hydrolase (NTPase) and RNA helicase activities that can hydrolyze all types of NTPs and unwind RNA helices dependently of the presence of NTP, and further characterize the biochemical characteristics of these two enzymatic activities associated with SARS-CoV-2 nsp13. Moreover, we found that some bismuth salts could effectively inhibit both the NTPase and RNA helicase activities of SARS-CoV-2 nsp13 in a dose-dependent manner. Thus, our findings demonstrate the NTPase and helicase activities of SARS-CoV-2 nsp13, which may play an important role in SARS-CoV-2 replication and serve as a target for antivirals.
- SARS-coronavirus-2 (SARS-CoV-2)
- , Nsp13
- , NTPase
- , Helicase
- , Antiviral target

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