Modulating SARS-CoV-2 Spike Protein Reactivity through Moderate Electric Fields: A Pathway to Innovative Therapies

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Abstract

In the quest for effective COVID-19 treatments and vaccines, traditional biochemical methods have been paramount, yet the challenge of accommodating diverse viral mutants persists. Recent simulations propose an innovative physical strategy involving an external electric field applied to the SARS-CoV-2 spike protein, demonstrating a reduced viral binding potential. However, limited empirical knowledge exists regarding the characteristics of the spike protein after E-field treatment. Our study addresses this gap by employing diverse analytical techniques to elucidate the impact of low/moderate E-field intensity on the binding of the SARS-CoV-2 spike protein to the ACE2 receptor. Through comprehensive analysis, we unveil a substantial reduction in the spike protein binding capacity validated via enzyme-linked immunosorbent assay and quartz crystal microbalance experiments. Remarkably, the E-field exposure induces significant protein structure rearrangement, leading to an enhanced negative surface zeta potential confirmed by dynamic light scattering. Circular dichroism spectroscopy corroborates these structural changes, showing alterations in the secondary protein structures. This study provides insights into SARS-CoV-2 spike protein modification under an E-field pulse, potentially paving the way for nonbiochemical strategies to mitigate viral reactivity and opening avenues for innovative therapeutic and preventive approaches against COVID-19 and its evolving variants.

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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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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Markus Hoffmann, Hannah Kleine-Weber, Simon Schroeder … (2020)

Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

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Author and article information

Journal

Journal ID (nlm-ta): ACS Omega

Journal ID (iso-abbrev): ACS Omega

Journal ID (publisher-id): ao

Journal ID (coden): acsodf

Title: ACS Omega

Publisher: American Chemical Society

ISSN (Electronic): 2470-1343

Publication date (Electronic): 21 November 2023

Publication date Collection: 05 December 2023

Volume: 8

Issue: 48

Pages: 45952-45960

Affiliations

[† ]Institute for Bioprocessing and Analytical Measurement Techniques , 37308 Heilbad Heiligenstadt, Germany

[‡ ]Faculty of Mathematics and Natural Sciences, Technische Universität Ilmenau , 98694 Ilmenau, Germany

[§ ]Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology , 07743 Jena, Germany

[∥ ]Institute of Microbiology, Friedrich-Schiller-Universität , 07743 Jena, Germany

Author notes

[* ]Email: thi-huong.nguyen@ 123456iba-heiligenstadt.de . Phone: +49(0)3606/671-600.

[* ]Email: Uwe.Pliquett@ 123456iba-heiligenstadt.de . Phone: +49(0)3606/671-315.

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Thi-Huong Nguyen https://orcid.org/0000-0002-9237-3482

Article

DOI: 10.1021/acsomega.3c06811

PMC ID: 10702300

PubMed ID: 38075772

SO-VID: 0f3607e5-4ece-496f-9f00-b47914fe92b7

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Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works ( https://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 07 September 2023

Date accepted : 02 November 2023

Date revision received : 31 October 2023

Funding

Funded by: Freistaat ThÃƒÂ¼ringen, doi 10.13039/100016019;

Award ID: NA

Funded by: Deutsche Forschungsgemeinschaft, doi 10.13039/501100001659;

Award ID: Project number: 469240103)

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document-id-new-14 ao3c06811

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Modulating SARS-CoV-2 Spike Protein Reactivity through Moderate Electric Fields: A Pathway to Innovative Therapies

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Novel Coronavirus Disease COVID-19

Most cited references 32

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

A Novel Coronavirus from Patients with Pneumonia in China, 2019

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

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