Humanized COVID‐19 decoy antibody effectively blocks viral entry and prevents SARS‐CoV‐2 infection

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Abstract

To circumvent the devastating pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, a humanized decoy antibody (ACE2‐Fc fusion protein) was designed to target the interaction between viral spike protein and its cellular receptor, angiotensin‐converting enzyme 2 (ACE2). First, we demonstrated that ACE2‐Fc could specifically abrogate virus replication by blocking the entry of SARS‐CoV‐2 spike‐expressing pseudotyped virus into both ACE2‐expressing lung cells and lung organoids. The impairment of viral entry was not affected by virus variants, since efficient inhibition was also observed in six SARS‐CoV‐2 clinical strains, including the D614G variants which have been shown to exhibit increased infectivity. The preservation of peptidase activity also enables ACE2‐Fc to reduce the angiotensin II‐mediated cytokine cascade. Furthermore, this Fc domain of ACE2‐Fc was shown to activate NK cell degranulation after co‐incubation with Spike‐expressing H1975 cells. These promising characteristics potentiate the therapeutic prospects of ACE2‐Fc as an effective treatment for COVID‐19.

Abstract

Currently, there is no effective strategy to fight against the COVID‐19 pandemic. We aim to design and develop a humanized decoy antibody to block SARS‐CoV‐2 infection.

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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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Clinical Characteristics of Coronavirus Disease 2019 in China

Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)

Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)

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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

Contributors

Sui‐Yuan Chang:

ORCID: https://orcid.org/0000-0002-6009-6724

sychang@ntu.edu.tw

Pan‐Chyr Yang:

ORCID: https://orcid.org/0000-0001-6330-6048

pcyang@ntu.edu.tw

Journal

Journal ID (nlm-ta): EMBO Mol Med

Journal ID (iso-abbrev): EMBO Mol Med

Journal ID (doi): 10.1002/(ISSN)1757-4684

Journal ID (publisher-id): EMMM

Journal ID (hwp): embomm

Title: EMBO Molecular Medicine

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 1757-4676

ISSN (Electronic): 1757-4684

Publication date (Electronic): 30 November 2020

Publication date (Print): 11 January 2021

Volume: 13

Issue: 1 ( doiID: 10.1002/emmm.v13.1 )

Electronic Location Identifier: e12828

Affiliations

[ ¹ ] Institute of Biomedical Sciences Academia Sinica Taipei Taiwan

[ ² ] Department of Internal Medicine National Taiwan University Hospital and National Taiwan University College of Medicine Taipei Taiwan

[ ³ ] Biomedical Translation Research Center (BioTReC) Academia Sinica Taipei Taiwan

[ ⁴ ] Department of Clinical Laboratory Sciences and Medical Biotechnology National Taiwan University College of Medicine Taipei Taiwan

[ ⁵ ] Institute of Biological Chemistry Academia Sinica Taipei Taiwan

[ ⁶ ] Institute of Biochemical Sciences National Taiwan University Taipei Taiwan

[ ⁷ ] Department of Laboratory Medicine National Taiwan University Hospital Taipei Taiwan

[ ⁸ ] Genomics Research Center Academia Sinica Taipei Taiwan

Author notes

[*] [* ] Corresponding author. Tel: +886 2 312 3456; E‐mail: sychang@ 123456ntu.edu.tw

Corresponding author: Tel: +886 2 23562905; E‐mail: pcyang@ 123456ntu.edu.tw

Author information

Sui‐Yuan Chang https://orcid.org/0000-0002-6009-6724

Pan‐Chyr Yang https://orcid.org/0000-0001-6330-6048

Article

Publisher ID: EMMM202012828

DOI: 10.15252/emmm.202012828

PMC ID: 7799362

PubMed ID: 33159417

SO-VID: 8a4acf74-75c4-4de2-adeb-bc20ea32426a

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

History

Date received : 27 May 2020

Date revision received : 03 November 2020

Date accepted : 05 November 2020

Page count

Figures: 15, Tables: 0, Pages: 19, Words: 21635

Funding

Funded by: Academia Sinica , open-funder-registry 10.13039/501100001869;

Award ID: AS‐SUMMIT‐108; AS‐SUMMIT‐109; AS‐KPQ‐109‐BioMed

Funded by: Ministry of Science and Technology, Taiwan (MOST) , open-funder-registry 10.13039/501100004663;

Award ID: MOST 107‐0210‐01‐19‐01

Award ID: MOST 108‐3114‐Y‐001‐002, MOST 109‐2314‐B‐002‐254, MOST 109‐2314‐B‐002‐277 and MOST 109‐2124‐M‐002‐012‐, MOST 107‐2320‐B‐002‐016‐MY3, MOST 109‐2327‐B‐002‐009

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cover-date 11 January 2021

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.6 mode:remove_FC converted:11.01.2021

ScienceOpen disciplines: Molecular medicine

Keywords: ace2‐fc,covid‐19,decoy antibody,sars‐cov‐2,virus infection,immunology,microbiology, virology & host pathogen interaction

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ScienceOpen disciplines: Molecular medicine

Keywords: ace2‐fc, covid‐19, decoy antibody, sars‐cov‐2, virus infection, immunology, microbiology, virology & host pathogen interaction

Humanized COVID‐19 decoy antibody effectively blocks viral entry and prevents SARS‐CoV‐2 infection

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Novel Coronavirus Disease COVID-19

Most cited references 41

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

Clinical Characteristics of Coronavirus Disease 2019 in China

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

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