SARS-CoV-2 and Three Related Coronaviruses Utilize Multipke ACE2 Orthologs and Are Potently Blocked by an Improved ACE2-Ig
文献类型：期刊论文
| 作者 | Li, Yujun1; Wang, Haimin1; Tang, Xiaojuan1; Fang, Shisong3; Ma, Danting1; Du, Chengzhi1,2; Wang, Yifei1; Pan, Hong1,2; Yao, Weitong1,2; Zhang, Renli3 |
| 刊名 | JOURNAL OF VIROLOGY
 |
| 出版日期 | 2020-11-01 |
| 卷号 | 94期号:22页码:14 |
| 关键词 | ACE2 ACE2-Ig SARS-CoV-2 entry inhibitor host range |
| ISSN号 | 0022-538X |
| DOI | 10.1128/JVI.01283-20 |
| 通讯作者 | Zhong, Guocai(zhonggc@szbl.ac.cn) |
| 英文摘要 | The ongoing coronavirus disease 2019 (COVID-19) pandemic has caused >20 million infections and >750,000 deaths. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, has been found closely related to the bat coronavirus strain RaTG13 (Bat-CoV RaTG13) and a recently identified pangolin coronavirus (Pangolin-CoV-2020). Here, we first investigated the ability of SARS-CoV-2 and three related coronaviruses to utilize animal orthologs of angiotensin-converting enzyme 2 (ACE2) for cell entry. We found that ACE2 orthologs of a wide range of domestic and wild mammals, including camels, cattle, horses, goats, sheep, cats, rabbits, and pangolins, were able to support cell entry of SARS-CoV-2, suggesting that these species might be able to harbor and spread this virus. In addition, the pangolin and bat coronaviruses, Pangolin-CoV-2020 and Bat-CoV RaTG13, were also found able to utilize human ACE2 and a number of animalACE2 orthologs for cell entry, indicating risks of spillover of these viruses into humans in the future. We then developed potently anticoronavirus ACE2-Ig proteins that are broadly effective against the four distinct coronaviruses. In particular, through truncating ACE2 at its residue 740 but not 615, introducing a D3OE mutation, and adopting an antibody-like tetrameric-ACE2 configuration, we generated an ACE2-Ig variant that neutralizes SARS-CoV-2 at picomolar range. These data demonstrate that the improved ACE2-Ig variants developed in this study could potentially be developed to protect from SARS-CoV-2 and some other SARS-like viruses that might spillover into humans in the future. IMPORTANCE The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the currently uncontrolled coronavirus disease 2019 (COVID-19) pandemic. It is important to study the host range of SARS-CoV-2, because some domestic species might harbor the virus and transmit it back to humans. In addition, insight into the ability of SARS-CoV-2 and SARS-like viruses to utilize animal orthologs of the SARS-CoV-2 receptor ACE2 might provide structural insight into improving ACE2-based viral entry inhibitors. In this study, we found that ACE2 orthologs of a wide range of domestic and wild animals can support cell entry of SARS-CoV-2 and three related coronaviruses, providing insights into identifying animal hosts of these viruses. We also developed recombinant ACE2-Ig proteins that are able to potently block these viral infections, providing a promising approach to developing antiviral proteins broadly effective against these distinct coronaviruses. |
| WOS关键词 | RESPIRATORY-SYNDROME CORONAVIRUS ; SARS CORONAVIRUS ; RECEPTOR ; SPIKE ; OUTBREAK |
| 资助项目 | National Natural Science Foundation of China[8187631] ; Shenzhen Science and Technology Program, Shenzhen Science and Technology Innovation Commission[JCYJ20180307102005105] ; Guangdong Provincial Department of Science and Technology, Shenzhen Bay Laboratory COVID-19 Contingency Funds[2020B1111340063] ; Guangdong Provincial Department of Science and Technology, Shenzhen Bay Laboratory COVID-19 Contingency Funds[2020B1111340077] ; Guangdong Provincial Department of Science and Technology, Shenzhen Bay Laboratory COVID-19 Contingency Funds[2020B1111340078] ; Key Project of Shenzhen Science and Technology Innovation Commission[202002073000003] ; Shenzhen Bay Laboratory Startup Funds[21230041] |
| WOS研究方向 | Virology |
| 语种 | 英语 |
| WOS记录号 | WOS:000582729300019 |
| 出版者 | AMER SOC MICROBIOLOGY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/291075]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhong, Guocai |
| 作者单位 | 1.Shenzhen Bay Lab, Inst Chem Biol, Shenzhen, Peoples R China 2.Peking Univ, Sch Chem Biol & Biotechnol, Shenzhen Grad Sch, Shenzhen, Peoples R China 3.Shenzhen Ctr Dis Control & Prevent, Shenzhen, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 5.Wenzhou Med Univ, Sch Biomed Engn, Wenzhou, Peoples R China 6.Wenzhou Med Univ, Eye Hosp, Wenzhou, Peoples R China 7.Scripps Res Inst, Dept Immunol & Microbiol, Jupiter, FL USA |
| 推荐引用方式 GB/T 7714 | Li, Yujun,Wang, Haimin,Tang, Xiaojuan,et al. SARS-CoV-2 and Three Related Coronaviruses Utilize Multipke ACE2 Orthologs and Are Potently Blocked by an Improved ACE2-Ig[J]. JOURNAL OF VIROLOGY,2020,94(22):14. |
| APA | Li, Yujun.,Wang, Haimin.,Tang, Xiaojuan.,Fang, Shisong.,Ma, Danting.,...&Zhong, Guocai.(2020).SARS-CoV-2 and Three Related Coronaviruses Utilize Multipke ACE2 Orthologs and Are Potently Blocked by an Improved ACE2-Ig.JOURNAL OF VIROLOGY,94(22),14. |
| MLA | Li, Yujun,et al."SARS-CoV-2 and Three Related Coronaviruses Utilize Multipke ACE2 Orthologs and Are Potently Blocked by an Improved ACE2-Ig".JOURNAL OF VIROLOGY 94.22(2020):14. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。