An Antioxidant Enzyme Therapeutic for COVID‐19

Qin, Meng; Cao, Zi-Jun; Wen, Jing; Yu, Qingsong; Liu, Chaoyong; Wang, Fang; Jian-jun, Zhang; Yang, Fengmei; Li, Yanyan; Fishbein, Gregory A.; Yan, Sen; Xu, Bin; Hou, Yi; Ning, Zhenbo; Nie, Kaili; Jiang, Ni; Liu, Zhen; Wu, Jun; Yu, Yanting; Li, Heng; Zheng, Huiwen; Li, Jing; Jin, Weihua; Pang, Shen; Wang, Shuai; Chen, Jianfeng; Gan, Zhihua; He, Zhanlong; Lu, Yunfeng

doi:10.1002/adma.202004901

Cited by 67 publications

(41 citation statements)

References 42 publications

(59 reference statements)

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“…[ 2 ] Several approaches involving advanced materials are being explored for therapeutics for the treatment of COVID‐19. [ 3 ] While these efforts address the treatment side, advanced materials can also be used to create new paradigms in testing for the disease that can play a pivotal role in the combat against epidemics. A rapid detection of the infection would allow isolation of patients and contact tracing that can save lives and help resume economic activity.…”

Section: Figurementioning

confidence: 99%

Sensing of COVID‐19 Antibodies in Seconds via Aerosol Jet Nanoprinted Reduced‐Graphene‐Oxide‐Coated 3D Electrodes

et al. 2020

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Rapid diagnosis is critical for the treatment and prevention of diseases. An advanced nanomaterial‐based biosensing platform that detects COVID‐19 antibodies within seconds is reported. The biosensing platform is created by 3D nanoprinting of three‐dimensional electrodes, coating the electrodes by nanoflakes of reduced‐graphene‐oxide (rGO), and immobilizing specific viral antigens on the rGO nanoflakes. The electrode is then integrated with a microfluidic device and used in a standard electrochemical cell. When antibodies are introduced on the electrode surface, they selectively bind with the antigens, changing the impedance of the electrical circuit which is detected via impedance spectroscopy. Antibodies to SARS‐CoV‐2 spike S1 protein and its receptor‐binding‐domain (RBD) are detected at a limit‐of‐detection of 2.8 × 10−15 and 16.9 × 10−15 m, respectively, and read by a smartphone‐based user interface. The sensor can be regenerated within a minute by introducing a low‐pH chemistry that elutes the antibodies from the antigens, allowing successive sensing of test samples using the same sensor. Sensing of S1 and RBD antibodies is specific, which cross‐reacts neither with other antibodies such as RBD, S1, and nucleocapsid antibody nor with proteins such as interleukin‐6. The proposed sensing platform could also be useful to detect biomarkers for other infectious agents such as Ebola, HIV, and Zika.

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Section: Figurementioning

confidence: 99%

Sensing of COVID‐19 Antibodies in Seconds via Aerosol Jet Nanoprinted Reduced‐Graphene‐Oxide‐Coated 3D Electrodes

et al. 2020

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“…HSP90AA1 and seed gene CAT showed significant differential expression and a strong reduction in co-expression networks in infected hiPSC-CMs in our study. CAT is considered the most effective catalyst for the decomposition of H2O2, regulating the production of cytokines, protecting from oxidative injury, and repressing replication of SARS-CoV-2 [76].…”

Section: The Role Of Virus-infection Related Proteins From Ace2 Netwomentioning

confidence: 99%

ACE2 Interaction Networks in COVID-19: A Physiological Framework for Prediction of Outcome in Patients with Cardiovascular Risk Factors

Wicik

Eyileten

Jakubik

et al. 2020

JCM

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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019; COVID-19) is associated with adverse outcomes in patients with cardiovascular disease (CVD). The aim of the study was to characterize the interaction between SARS-CoV-2 and Angiotensin-Converting Enzyme 2 (ACE2) functional networks with a focus on CVD. Methods: Using the network medicine approach and publicly available datasets, we investigated ACE2 tissue expression and described ACE2 interaction networks that could be affected by SARS-CoV-2 infection in the heart, lungs and nervous system. We compared them with changes in ACE-2 networks following SARS-CoV-2 infection by analyzing public data of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). This analysis was performed using the Network by Relative Importance (NERI) algorithm, which integrates protein-protein interaction with co-expression networks. We also performed miRNA-target predictions to identify which miRNAs regulate ACE2-related networks and could play a role in the COVID19 outcome. Finally, we performed enrichment analysis for identifying the main COVID-19 risk groups. Results: We found similar ACE2 expression confidence levels in respiratory and cardiovascular systems, supporting that heart tissue is a potential target of SARS-CoV-2. Analysis of ACE2 interaction networks in infected hiPSC-CMs identified multiple hub genes with corrupted signaling which can be responsible for cardiovascular symptoms. The most affected genes were EGFR (Epidermal Growth Factor Receptor), FN1 (Fibronectin 1), TP53, HSP90AA1, and APP (Amyloid Beta Precursor Protein), while the most affected interactions were associated with MAST2 and CALM1 (Calmodulin 1). Enrichment analysis revealed multiple diseases associated with the interaction networks of ACE2, especially cancerous diseases, obesity, hypertensive disease, Alzheimer’s disease, non-insulin-dependent diabetes mellitus, and congestive heart failure. Among affected ACE2-network components connected with the SARS-Cov-2 interactome, we identified AGT (Angiotensinogen), CAT (Catalase), DPP4 (Dipeptidyl Peptidase 4), CCL2 (C-C Motif Chemokine Ligand 2), TFRC (Transferrin Receptor) and CAV1 (Caveolin-1), associated with cardiovascular risk factors. We described for the first time miRNAs which were common regulators of ACE2 networks and virus-related proteins in all analyzed datasets. The top miRNAs regulating ACE2 networks were miR-27a-3p, miR-26b-5p, miR-10b-5p, miR-302c-5p, hsa-miR-587, hsa-miR-1305, hsa-miR-200b-3p, hsa-miR-124-3p, and hsa-miR-16-5p. Conclusion: Our study provides a complete mechanistic framework for investigating the ACE2 network which was validated by expression data. This framework predicted risk groups, including the established ones, thus providing reliable novel information regarding the complexity of signaling pathways affected by SARS-CoV-2. It also identified miRNAs that could be used in personalized diagnosis in COVID-19.

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“…Cytokines suppressor [77] Enzyme CAT Antioxidant agent: cytokine production regulator through the GSH pathway [78] N-acetylcysteine (NAC) IL-6-inhibiting agent through the GSH pathway [66] The counterbalancing of oxidative stress is crucial in CSS [50] to prevent GSH depletion and its disastrous consequences [69]. Counterbalancing oxidative stress is also important in avoiding signal transduction pathways that stimulate pro-inflammatory cytokines production [66].…”

Section: Curcuminmentioning

confidence: 99%

“…As a result, treatments that are able to reduce ROS can help with treating CSS. The use of the enzyme CAT was proposed as CAT was to have an antiinflammatory effect by regulating cytokine production and providing protection against oxidative injury in human leukocytes and alveolar epithelial cells [78]. This enzyme is safe and commonly used as a food additive and dietary supplement.…”

Section: Curcuminmentioning

confidence: 99%

Sea Urchin Pigments: Echinochrome A and Its Potential Implication in the Cytokine Storm Syndrome

et al. 2021

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Background: Echinochrome A (EchA) is a pigment from sea urchins. EchA is a polyhydroxylated 1,4-naphthoquinone that contains several hydroxyl groups appropriate for free-radical scavenging and preventing redox imbalance. EchA is the most studied molecule of this family and is an active principle approved to be used in humans, usually for cardiopathies and glaucoma. EchA is used as a pharmaceutical drug. Methods: A comprehensive literature and patent search review was undertaken using PubMed, as well as Google Scholar and Espacenet search engines to review these areas. Conclusions: In the bloodstream, EchA can mediate cellular responses, act as a radical scavenger, and activate the glutathione pathway. It decreases ROS imbalance, prevents and limits lipid peroxidation, and enhances mitochondrial functions. Most importantly, EchA contributes to the modulation of the immune system. EchA can regulate the generation of regulatory T cells, inhibit pro-inflammatory IL-1β and IL-6 cytokine production, while slightly reducing IL-8, TNF-α, INF-α, and NKT, thus correcting immune imbalance. These characteristics suggest that EchA is a candidate drug to alleviate the cytokine storm syndrome (CSS).

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An Antioxidant Enzyme Therapeutic for COVID‐19

Cited by 67 publications

References 42 publications

Sensing of COVID‐19 Antibodies in Seconds via Aerosol Jet Nanoprinted Reduced‐Graphene‐Oxide‐Coated 3D Electrodes

Sensing of COVID‐19 Antibodies in Seconds via Aerosol Jet Nanoprinted Reduced‐Graphene‐Oxide‐Coated 3D Electrodes

ACE2 Interaction Networks in COVID-19: A Physiological Framework for Prediction of Outcome in Patients with Cardiovascular Risk Factors

Sea Urchin Pigments: Echinochrome A and Its Potential Implication in the Cytokine Storm Syndrome

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