Decoy nanoparticles protect against COVID-19 by concurrently adsorbing viruses and inflammatory cytokines

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The COVID-19 pandemic caused by SARS-CoV-2 infection has led to more than 840,000 deaths worldwide as of August 31, 2020. Unfortunately, no licensed vaccine or specific treatment is available right now. Herein, we report a decoy nanoparticle against COVID-19. The decoy nanoparticles were constructed by fusing cell membrane nanovesicles derived from genetically engineered cells, which stably express SARS-CoV-2 receptor ACE2, and human monocytes, which display abundant cytokine receptors. By competing with host cells, these nanodecoys efficiently adsorb viruses and inflammatory cytokines such as IL-6 and GM-CSF. These two functionalities allow effective intervention of viral infection and its associated immune disorder, presenting a promising therapeutic strategy for COVID-19 and other potential epidemics.

Abstract

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the urgent need to rapidly develop therapeutic strategies for such emerging viruses without effective vaccines or drugs. Here, we report a decoy nanoparticle against COVID-19 through a powerful two-step neutralization approach: virus neutralization in the first step followed by cytokine neutralization in the second step. The nanodecoy, made by fusing cellular membrane nanovesicles derived from human monocytes and genetically engineered cells stably expressing angiotensin converting enzyme II (ACE2) receptors, possesses an antigenic exterior the same as source cells. By competing with host cells for virus binding, these nanodecoys effectively protect host cells from the infection of pseudoviruses and authentic SARS-CoV-2. Moreover, relying on abundant cytokine receptors on the surface, the nanodecoys efficiently bind and neutralize inflammatory cytokines including interleukin 6 (IL-6) and granulocyte−macrophage colony-stimulating factor (GM-CSF), and significantly suppress immune disorder and lung injury in an acute pneumonia mouse model. Our work presents a simple, safe, and robust antiviral nanotechnology for ongoing COVID-19 and future potential epidemics.

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Most cited references 41

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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): Proc Natl Acad Sci U S A

Journal ID (iso-abbrev): Proc Natl Acad Sci U S A

Journal ID (hwp): pnas

Journal ID (pmc): pnas

Journal ID (publisher-id): PNAS

Title: Proceedings of the National Academy of Sciences of the United States of America

Publisher: National Academy of Sciences

ISSN (Print): 0027-8424

ISSN (Electronic): 1091-6490

Publication date (Print): 3 November 2020

Publication date (Electronic): 6 October 2020

Publication date PMC-release: 6 October 2020

Volume: 117

Issue: 44

Pages: 27141-27147

Affiliations

[1] ^aLaboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health , Bethesda, MD 20892;

[2] ^bBiosafety Level 3 Laboratory, Key Laboratory of Medical Molecular Virology (Ministry of Education/National Health Commission/Chinese Academy of Medical Sciences), School of Basic Medical Sciences, Fudan University , 200032 Shanghai, China;

[3] ^cInstitute of Medical Microbiology, Jinan University , 510632 Guangzhou, China;

[4] ^dState Key Laboratory of Virology, College of Life Sciences, Wuhan University , 430072 Wuhan, China;

[5] ^eSchool of Physics and Technology, Wuhan University , 430072 Wuhan, China

Author notes

²To whom correspondence may be addressed. Email: lul@ 123456fudan.edu.cn , yhxie@ 123456fudan.edu.cn , shibojiang@ 123456fudan.edu.cn , or chen9647@ 123456gmail.com .

Edited by Karen L. Wooley, Texas A&M University, College Station, TX, and approved September 11, 2020 (received for review July 8, 2020)

Author contributions: L.R. designed the research; L.R., S.X., W.X., R.T., G.Y., C.G., P.P., and Q.-F.M. performed the experiments; L.R., S.X., X. Cai, D.Q., L.L., Y.X., S.J., and X. Chen analyzed the data; and L.R., S.X., L.L., Y.X., S.J., and X. Chen wrote the paper.

¹L.R., S.X., and W.X. contributed equally to this work.

Author information

Lang Rao https://orcid.org/0000-0001-5010-0729

Lu Lu https://orcid.org/0000-0002-2255-0391

Xiaoyuan Chen https://orcid.org/0000-0002-9622-0870

Article

Publisher ID: 202014352

DOI: 10.1073/pnas.2014352117

PMC ID: 7959535

PubMed ID: 33024017

SO-VID: 8695f581-524b-45fe-b95b-17d47abf06a3

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This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).

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Pages: 7

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Funded by: HHS | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) 100000070

Decoy nanoparticles protect against COVID-19 by concurrently adsorbing viruses and inflammatory cytokines

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Most cited references 41

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

A Novel Coronavirus from Patients with Pneumonia in China, 2019

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

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