Proteomic and phosphoproteomic profiling of COVID-19-associated lung and liver injury: a report based on rhesus macaques

Liu, Jianfeng; Zhou, Yanan; Lu, Shuaiyao; Yang, Yehong; Wu, Songfeng; Liu, Depei; Liu, Hongqi; Yang, Juntao

doi:10.1038/s41392-022-00882-7

Cited by 16 publications

(12 citation statements)

References 6 publications

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“…These findings suggest therapeutic utility for PKC inhibitors against COVID-19 in humans with and without T2D. In particular, the pan-PKC inhibitor bisindolylmaleimide-IX seems promising as it was additionally demonstrated, by virtual screening and in vitro validation assays, to target the main SARS-CoV-2 protease 3CLpro [49] Importantly, similar to our study, another proteomic and phosphoproteomic study of COVID-19 in macaques identified members of the PKC and AMPK families activated in the liver, where these kinases play key metabolic roles [50] . These authors also found proliferation-related MAP2K2 to be activated in infected macaque lungs and drug enrichment analysis suggested that fostamatinib, an inhibitor of SYF used to treat thrombocytopenia, could be an effective drug against the activated kinases detected in both the lungs and liver [50] .…”

Section: Discussionsupporting

confidence: 75%

Extracellular vesicle proteomics and phosphoproteomics identify pathways for increased risk in patients hospitalized with COVID-19 and type 2 diabetes mellitus

Lopez¹,

Iliuk²,

Casu³

et al. 2023

Diabetes Research and Clinical Practice

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Section: Discussionsupporting

confidence: 75%

Extracellular vesicle proteomics and phosphoproteomics identify pathways for increased risk in patients hospitalized with COVID-19 and type 2 diabetes mellitus

Lopez¹,

Iliuk²,

Casu³

et al. 2023

Diabetes Research and Clinical Practice

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“…Pyronaridine preferentially associates with blood cells and is highly plasma protein bound, which suggests that it may not reach the unbound concentration necessary to have an effect on PL pro and CAMK1 at these doses. Activation of CAMK1 has been reported to negatively impact HBV biosynthesis. , Inhibition of CAMK1 might not however be therapeutically relevant since reports on proteomic and phosphoproteomic profiling of COVID-19 and phosphorylation landscape for SARS-CoV-2 infection do not point to an important role of this kinase on COVID-19. Currently, Shin Poong Pharmaceutical Co. Ltd. is recruiting patients for phase III clinical trials for COVID-19 ( Identifier: NCT05084911) using a combination of pyronaridine and artesunate.…”

Section: Resultsmentioning

confidence: 99%

Pyronaridine Protects against SARS-CoV-2 Infection in Mouse

et al. 2022

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There are currently relatively few small-molecule antiviral drugs that are either approved or emergency-approved for use against severe acute respiratory coronavirus 2 (SARS-CoV-2). One of these is remdesivir, which was originally repurposed from its use against Ebola. We evaluated three molecules we had previously identified computationally with antiviral activity against Ebola and Marburg and identified pyronaridine, which inhibited the SARS-CoV-2 replication in A549-ACE2 cells. The in vivo efficacy of pyronaridine has now been assessed in a K18-hACE transgenic mouse model of COVID-19. Pyronaridine treatment demonstrated a statistically significant reduction of viral load in the lungs of SARS-CoV-2-infected mice, reducing lung pathology, which was also associated with significant reduction in the levels of pro-inflammatory cytokines/chemokine and cell infiltration. Pyronaridine inhibited the viral PL pro activity in vitro (IC 50 of 1.8 μM) without any effect on M pro , indicating a possible molecular mechanism involved in its ability to inhibit SARS-CoV-2 replication. We have also generated several pyronaridine analogs to assist in understanding the structure activity relationship for PL pro inhibition. Our results indicate that pyronaridine is a potential therapeutic candidate for COVID-19.

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“…A few studies have investigated the proteomic characteristics and changes in COVID-19 patients in plasma, BAL, sputum and pulmonary tissue [ 8 – 11 ]. Yet, none have yet investigated the proteomic profile of COVID-19 in EBPs.…”

Section: Introductionmentioning

confidence: 99%

Proteomic characteristics and diagnostic potential of exhaled breath particles in patients with COVID-19

et al. 2023

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Background SARS-CoV-2 has been shown to predominantly infect the airways and the respiratory tract and too often have an unpredictable and different pathologic pattern compared to other respiratory diseases. Current clinical diagnostical tools in pulmonary medicine expose patients to harmful radiation, are too unspecific or even invasive. Proteomic analysis of exhaled breath particles (EBPs) in contrast, are non-invasive, sample directly from the pathological source and presents as a novel explorative and diagnostical tool. Methods Patients with PCR-verified COVID-19 infection (COV-POS, n = 20), and patients with respiratory symptoms but with > 2 negative polymerase chain reaction (PCR) tests (COV-NEG, n = 16) and healthy controls (HCO, n = 12) were prospectively recruited. EBPs were collected using a “particles in exhaled air” (PExA 2.0) device. Particle per exhaled volume (PEV) and size distribution profiles were compared. Proteins were analyzed using liquid chromatography-mass spectrometry. A random forest machine learning classification model was then trained and validated on EBP data achieving an accuracy of 0.92. Results Significant increases in PEV and changes in size distribution profiles of EBPs was seen in COV-POS and COV-NEG compared to healthy controls. We achieved a deep proteome profiling of EBP across the three groups with proteins involved in immune activation, acute phase response, cell adhesion, blood coagulation, and known components of the respiratory tract lining fluid, among others. We demonstrated promising results for the use of an integrated EBP biomarker panel together with particle concentration for diagnosis of COVID-19 as well as a robust method for protein identification in EBPs. Conclusion Our results demonstrate the promising potential for the use of EBP fingerprints in biomarker discovery and for diagnosing pulmonary diseases, rapidly and non-invasively with minimal patient discomfort.

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Proteomic and phosphoproteomic profiling of COVID-19-associated lung and liver injury: a report based on rhesus macaques

Cited by 16 publications

References 6 publications

Extracellular vesicle proteomics and phosphoproteomics identify pathways for increased risk in patients hospitalized with COVID-19 and type 2 diabetes mellitus

Extracellular vesicle proteomics and phosphoproteomics identify pathways for increased risk in patients hospitalized with COVID-19 and type 2 diabetes mellitus

Pyronaridine Protects against SARS-CoV-2 Infection in Mouse

Proteomic characteristics and diagnostic potential of exhaled breath particles in patients with COVID-19

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