Single-nucleus lung transcriptomics and inflammatory responses in lethal COVID-19 reveal potential drugs in advanced-stage clinical trials Article Swipe
Andrés López‐Cortés
,
Santiago Guerrero
,
Esteban Ortiz‐Prado
,
Verónica Yumiceba
,
Antonella Vera-Gupi
,
Ángela León Cáceres
,
Katherine Simbaña‐Rivera
,
Ana María Gómez-Jaramillo
,
Patricia Guevara-Ramírez
,
Jennyfer M. García-Cárdenas
,
Alejandro Cabrera‐Andrade
,
Gabriela Echeverría‐Garcés
,
Lourdes Puig San Andrés
,
Doménica Cevallos-Robalino
,
Jhommara Bautista
,
Isaac Armendáriz‐Castillo
,
Andy Pérez‐Villa
,
Andrea Abad-Sojos
,
María José Ramos-Medina
,
Ariana León-Sosa
,
Estefanía Abarca
,
Álvaro A. Pérez-Meza
,
Karol Nieto-Jaramillo
,
Andrea V. Jácome
,
Andrea Macía Morillo
,
Fernanda Arias-Erazo
,
Luis Fuenmayor-González
,
Nikolaos C. Kyriakidis
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-808746/v1
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-808746/v1
There is pressing urgency to identify drugs that allow treating COVID-19 patients effectively. Respiratory failure is the leading cause of death in patients with severe COVID-19, and the host inflammatory response at the lungs remains poorly understood. Therefore, we retrieved data from postmortem lungs from COVID-19 patients and performed in-depth in silico analyses of single-nucleus RNA sequencing data, inflammatory protein interactome network, functional enrichment, and shortest pathways to cancer hallmark phenotypes to reveal potential therapeutic targets and drugs in advanced-stage COVID-19 clinical trials. Herein, we analyzed transcriptomics data of 719 inflammatory response genes across 19 cell types (116,313 nuclei) from lung autopsies. The functional enrichment analysis of the 233 significantly expressed genes showed that the most relevant biological annotations were: inflammatory response, innate immune response, cytokine production, interferon production, macrophage activation, thymic stromal lymphopoietin, blood coagulation, IL-1 and megakaryocytes in obesity, NLRP3 inflammasome complex, and the TLR, JAK-STAT, NF- κ B, TNF, oncostatin M, AGE-RAGE signaling pathways. Subsequently, we identified 34 essential inflammatory proteins with both high-confidence protein interactions and shortest pathways to inflammation, cell death, glycolysis, and angiogenesis. Lastly, we propose five small molecules involved in advanced-stage COVID-19 clinical trials: baricitinib, pacritinib, and ruxolitinib are tyrosine-protein kinase JAK2 inhibitors, losmapimod is a MAP kinase p38 alpha inhibitor, and eritoran is a TLR4/MD-2 antagonist. After being thoroughly analyzed in COVID-19 clinical trials, these drugs can be considered for treating severe COVID-19 patients.
Related Topics
Concepts
Coronavirus disease 2019 (COVID-19)
Transcriptome
Stage (stratigraphy)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
2019-20 coronavirus outbreak
Lung
Clinical trial
Medicine
Biology
Pathology
Internal medicine
Genetics
Gene
Outbreak
Disease
Gene expression
Infectious disease (medical specialty)
Paleontology
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-808746/v1
- https://www.researchsquare.com/article/rs-808746/latest.pdf
- OA Status
- green
- Cited By
- 1
- References
- 128
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3195227365
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3195227365Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.21203/rs.3.rs-808746/v1Digital Object Identifier
- Title
-
Single-nucleus lung transcriptomics and inflammatory responses in lethal COVID-19 reveal potential drugs in advanced-stage clinical trialsWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-08-17Full publication date if available
- Authors
-
Andrés López‐Cortés, Santiago Guerrero, Esteban Ortiz‐Prado, Verónica Yumiceba, Antonella Vera-Gupi, Ángela León Cáceres, Katherine Simbaña‐Rivera, Ana María Gómez-Jaramillo, Patricia Guevara-Ramírez, Jennyfer M. García-Cárdenas, Alejandro Cabrera‐Andrade, Gabriela Echeverría‐Garcés, Lourdes Puig San Andrés, Doménica Cevallos-Robalino, Jhommara Bautista, Isaac Armendáriz‐Castillo, Andy Pérez‐Villa, Andrea Abad-Sojos, María José Ramos-Medina, Ariana León-Sosa, Estefanía Abarca, Álvaro A. Pérez-Meza, Karol Nieto-Jaramillo, Andrea V. Jácome, Andrea Macía Morillo, Fernanda Arias-Erazo, Luis Fuenmayor-González, Nikolaos C. KyriakidisList of authors in order
- Landing page
-
https://doi.org/10.21203/rs.3.rs-808746/v1Publisher landing page
- PDF URL
-
https://www.researchsquare.com/article/rs-808746/latest.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.researchsquare.com/article/rs-808746/latest.pdfDirect OA link when available
- Concepts
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Coronavirus disease 2019 (COVID-19), Transcriptome, Stage (stratigraphy), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 2019-20 coronavirus outbreak, Lung, Clinical trial, Medicine, Biology, Pathology, Internal medicine, Genetics, Gene, Outbreak, Disease, Gene expression, Infectious disease (medical specialty), PaleontologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
- Citations by year (recent)
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2022: 1Per-year citation counts (last 5 years)
- References (count)
-
128Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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