A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2

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Abstract

Developing therapeutics against SARS-CoV-2 could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein, but also across the full Spike (S) protein. We isolated and characterized monoclonal antibodies (mAbs) from ten convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. An mAb, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2, but does not bind the RBD. We defined the epitope of 4A8 as the N terminal domain (NTD) of the S protein by determining its cryo-EM structure in complex with the S protein to an overall resolution of 3.1 Angstrom and local resolution of 3.3 Angstrom for the 4A8-NTD interface. This points to the NTD as a promising target for therapeutic mAbs against COVID-19.

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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang, Yeming Wang, Xingwang Li … (2020)

Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

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A Novel Coronavirus from Patients with Pneumonia in China, 2019

Na Zhu, Dingyu Zhang, Wenling Wang … (2020)

Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)

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A pneumonia outbreak associated with a new coronavirus of probable bat origin

Peng Zhou, Xing-Lou Yang, Xian-Guang Wang … (2020)

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.

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Author and article information

Journal

Journal ID (nlm-ta): Science

Journal ID (iso-abbrev): Science

Journal ID (publisher-id): SCIENCE

Title: Science (New York, N.y.)

Publisher: American Association for the Advancement of Science

ISSN (Print): 0036-8075

ISSN (Electronic): 1095-9203

Publication date (Electronic): 22 June 2020

Electronic Location Identifier: eabc6952

Affiliations

[1 ]Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.

[2 ]Key Laboratory of Structural Biology of Zhejiang Province, Institute of Biology, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang Province, China.

[3 ]Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.

Author notes

[*]

These authors contributed equally to this work.

[† ]Corresponding author. Email: cw0226@ 123456foxmail.com (W.C.); zhouqiang@ 123456westlake.edu.cn (Q.Z.); lijmqz@ 123456126.com (J.L.)

Author information

Xiangyang Chi https://orcid.org/0000-0002-0580-5997

Renhong Yan https://orcid.org/0000-0002-7122-6547

Jun Zhang https://orcid.org/0000-0002-9650-112X

Guanying Zhang https://orcid.org/0000-0003-3372-3355

Yuanyuan Zhang https://orcid.org/0000-0002-2500-0010

Meng Hao https://orcid.org/0000-0002-1258-6825

Zhe Zhang https://orcid.org/0000-0002-9303-8221

Pengfei Fan https://orcid.org/0000-0002-7212-231X

Yunzhu Dong https://orcid.org/0000-0003-4266-7295

Yilong Yang https://orcid.org/0000-0003-3412-0425

Zhengshan Chen https://orcid.org/0000-0003-2869-1467

Yingying Guo https://orcid.org/0000-0001-6261-0435

Jinlong Zhang https://orcid.org/0000-0001-9427-2645

Yaning Li https://orcid.org/0000-0003-3245-3023

Xiaohong Song https://orcid.org/0000-0002-7092-2639

Yi Chen https://orcid.org/0000-0002-8820-2904

Lu Xia https://orcid.org/0000-0003-3007-3086

Ling Fu https://orcid.org/0000-0002-5918-3978

Lihua Hou https://orcid.org/0000-0003-3644-2612

Junjie Xu https://orcid.org/0000-0001-5456-837X

Changming Yu https://orcid.org/0000-0002-0304-4477

Jianmin Li https://orcid.org/0000-0002-2827-2185

Qiang Zhou https://orcid.org/0000-0002-6237-8813

Wei Chen https://orcid.org/0000-0001-5805-2469

Article

Publisher ID: abc6952

DOI: 10.1126/science.abc6952

PMC ID: 7319273

PubMed ID: 32571838

SO-VID: abb8bb9c-34ed-47f0-890d-8898cede9c6c

Copyright © Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

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This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.