A 3D structural SARS-CoV-2–human interactome to explore genetic and drug perturbations

Wierbowski, Shayne D.; Liang, Siqi; Liu, Yuan; Chen, You; Gupta, Shagun; André, Nicole M.; Sm, Lipkin; Whittaker, Gary R.; Yu, Haiyuan

doi:10.1038/s41592-021-01318-w

Cited by 18 publications

(21 citation statements)

References 120 publications

(147 reference statements)

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“…Our state-of-the-art knowledge about the SARS-CoV-2's disease is that the SARS-CoV-2 virus is more stable than the SARS-CoV virus (Van Doremalen et al, 2020) and has a more flexible spike-protein that facilitates human cells infection (Turoňová et al, 2020;Ahn et al, 2021). Bioinformatic calculations (Cava et al, 2020;Wierbowski et al, 2021) and affinity purification mass spectrometry (Gordon et al, 2020;Wierbowski et al, 2021) were two key technologies that helped scientists identify SARS-CoV-2 proteins (and their active sites) that interact with their host during its life cycle and identify therapeutic targets for developing antiviral drugs to treat COVID-19 patients (Gordon et al, 2020). For example, antiviral compounds against COVID-19 target the active sites of enzymes involved in the virus's replication cycle (Mehta et al, 2020;Riva et al, 2020;Shannon et al, 2020;Shi and Puyo, 2020;Wang et al, 2020;Bakowski et al, 2021).…”

Section: Ms For Understanding the Covid-19 Diseasementioning

confidence: 99%

“…Thus, there has been a surge in the development of MS-based strategies for diagnosing COVID-19 disease from an exhaled breath, a nasopharyngeal swab, or a gargle solution (Cardozo et al, 2020;Ihling et al, 2020;Nachtigall et al, 2020;Ruszkiewicz et al, 2020;Bankar et al, 2021;Chen et al, 2021;Maus et al, 2021;Renuse et al, 2021;Tran et al, 2021). Furthermore, an exciting research line has focused on identifying biomarkers that reflect the severe COVID-19 phenotype (Chen et al, 2020a;Gordon et al, 2020;Kimhofer et al, 2020;Messner et al, 2020;Shen et al, 2020;Wu et al, 2020;Chevrier et al, 2021;Holmes et al, 2021;Lee et al, 2021;Messner et al, 2021;Wierbowski et al, 2021;Zhang et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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How Is Mass Spectrometry Tackling the COVID-19 Pandemic?

Ibáñez

2022

Front. Anal. Sci.

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Most of us have never faced a pandemic before. The World Health Organization declared the 2019 novel coronavirus infectious disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus), a pandemic by March 11th, 2020. Today, this illness has reported more than 5′331,019 fatalities worldwide (December 17th, 2021). The COVID-19 pandemic has posed an unprecedented global challenge and put the academic community on “the spot.” The following mini-review reports how the MS community improved the understanding of the SARS-CoV-2 virus pathophysiology while developing diagnostic procedures to complement the PCR-based approaches. For example, MS researchers identified the interaction sites between the SARS-CoV-2 virus and their hosts; this new knowledge is critical for developing antiviral drugs. MS researchers also realized that COVID-19 should be considered a systemic disease and not just a respiratory illness since its metabolic, lipidomic, and proteomic profile reflects four different clinical disorders: 1) acute inflammatory response, 2) a cardiovascular disease, 3) a prediabetic/diabetes and 4) liver dysfunction. Furthermore, MS researchers put forth the knowledge that the metabolic and lipidomic profile of several patients remained altered after being discharged, thus hinting at the scientific basis for the long COVID syndrome.

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Section: Ms For Understanding the Covid-19 Diseasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

How Is Mass Spectrometry Tackling the COVID-19 Pandemic?

Ibáñez

2022

Front. Anal. Sci.

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“…Furthermore, the integration of interactome data with available proteomic, genetic, structural and clinical data can give a more comprehensive picture of the biological process perturbed during viral infection, paving the way to the identification of novel drug targets and successful treatments ( Bouhaddou et al, 2020 ; Gordon et al, 2020b ; Wierbowski et al, 2021 ).…”

Section: Conclusion and Future Challengesmentioning

confidence: 99%

“…In-silico approaches based on sequence (e.g., Eid et al, 2016 ; Liu-Wei et al, 2021 ) and structural similarity (e.g., de Chassey et al, 2013 ; Lasso et al, 2019 ), as well as protein docking ( Wierbowski et al, 2021 ), have been also used to predict virus-host protein-protein interactions. The recent advent of deep-learning methods to predict protein structures ( Senior et al, 2020 ; Baek et al, 2021 ) as well as protein macromolecular complexes ( Baek et al, 2021 ; Bryant et al, 2021 ; Evans et al, 2021 ), can be a useful complementary strategy to identify or validate the molecular determinants of virus-host protein interactions identified in experimental assays.…”

Section: Main Limitations Of Protein-protein Interaction Data and The...mentioning

confidence: 99%

The Intricacy of the Viral-Human Protein Interaction Networks: Resources, Data, and Analyses

et al. 2022

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Viral infections are one of the major causes of human diseases that cause yearly millions of deaths and seriously threaten global health, as we have experienced with the COVID-19 pandemic. Numerous approaches have been adopted to understand viral diseases and develop pharmacological treatments. Among them, the study of virus-host protein-protein interactions is a powerful strategy to comprehend the molecular mechanisms employed by the virus to infect the host cells and to interact with their components. Experimental protein-protein interactions described in the scientific literature have been systematically captured into several molecular interaction databases. These data are organized in structured formats and can be easily downloaded by users to perform further bioinformatic and network studies. Network analysis of available virus-host interactomes allow us to understand how the host interactome is perturbed upon viral infection and what are the key host proteins targeted by the virus and the main cellular pathways that are subverted. In this review, we give an overview of publicly available viral-human protein-protein interactions resources and the community standards, curation rules and adopted ontologies. A description of the main virus-human interactome available is provided, together with the main network analyses that have been performed. We finally discuss the main limitations and future challenges to assess the quality and reliability of protein-protein interaction datasets and resources.

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“…A relevant example of such integrated approaches is the recent development of the 3D-SARS2 structural interactome browser by Wierbowski and coworkers [ 94 ]. To facilitate the exploration of how pathogen–host interactions might affect SARS-CoV-2 transmission and virulence, they performed interface prediction followed by molecular docking to generate a 3D structural interactome between SARS-CoV-2 and a human.…”

Section: Perspectives and Future Directionsmentioning

confidence: 99%

Looking at COVID-19 from a Systems Biology Perspective

2022

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The sudden outbreak and worldwide spread of the SARS-CoV-2 pandemic pushed the scientific community to find fast solutions to cope with the health emergency. COVID-19 complexity, in terms of clinical outcomes, severity, and response to therapy suggested the use of multifactorial strategies, characteristic of the network medicine, to approach the study of the pathobiology. Proteomics and interactomics especially allow to generate datasets that, reduced and represented in the forms of networks, can be analyzed with the tools of systems biology to unveil specific pathways central to virus–human host interaction. Moreover, artificial intelligence tools can be implemented for the identification of druggable targets and drug repurposing. In this review article, we provide an overview of the results obtained so far, from a systems biology perspective, in the understanding of COVID-19 pathobiology and virus–host interactions, and in the development of disease classifiers and tools for drug repurposing.

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A 3D structural SARS-CoV-2–human interactome to explore genetic and drug perturbations

Cited by 18 publications

References 120 publications

How Is Mass Spectrometry Tackling the COVID-19 Pandemic?

How Is Mass Spectrometry Tackling the COVID-19 Pandemic?

The Intricacy of the Viral-Human Protein Interaction Networks: Resources, Data, and Analyses

Looking at COVID-19 from a Systems Biology Perspective

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