scholarly journals A system biology approach identifies candidate drugs to reduce mortality in severely ill COVID-19 patients

2021 ◽  
Author(s):  
Vinicius M Fava ◽  
Mathieu Bourgey ◽  
Pubudu M. Nawarathna ◽  
Marianna Orlova ◽  
Pauline Cassart ◽  
...  
Keyword(s):  
Hospital Admission ◽  
Rna Splicing ◽  
Drug Targets ◽  
System Biology ◽  
High Rate ◽  
Host Responses ◽  
Ordinal Scale ◽  
System Biology Approach ◽  
Interferon Signaling ◽  
Mrna Metabolism

Despite the availability of highly efficacious vaccines, Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) lacks effective drug treatment which results in a high rate of mortality. To address this therapeutic shortcoming, we applied a system biology approach to the study of patients hospitalized with severe COVID. We show that, at the time of hospital admission, patients who were equivalent on the clinical ordinal scale displayed significant differential monocyte epigenetic and transcriptomic attributes between those who would survive and those who would succumb to COVID-19. We identified mRNA metabolism, RNA splicing, and interferon signaling pathways as key host responses overactivated by patients who would not survive. Those pathways are prime drug targets to reduce mortality of critically ill COVID-19 patients leading us to identify Tacrolimus, Zotatifin, and Nintedanib as three strong candidates for treatment of severely ill patients at the time of hospital admission.

scholarly journals Transcriptional and proteomic insights into the host response in fatal COVID-19 cases

2020 ◽  
Vol 117 (45) ◽  
pp. 28336-28343 ◽  
Author(s):  
Meng Wu ◽  
Yaobing Chen ◽  
Han Xia ◽  
Changli Wang ◽  
Chin Yee Tan ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Host Response ◽  
Drug Targets ◽  
Potential Role ◽  
Host Responses ◽  
Human Lung Tissue ◽  
Proteomics Analysis ◽  
Global Pandemic ◽  
A Site ◽  
Potential Drug Targets

Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, has resulted thus far in greater than 933,000 deaths worldwide; yet disease pathogenesis remains unclear. Clinical and immunological features of patients with COVID-19 have highlighted a potential role for changes in immune activity in regulating disease severity. However, little is known about the responses in human lung tissue, the primary site of infection. Here we show that pathways related to neutrophil activation and pulmonary fibrosis are among the major up-regulated transcriptional signatures in lung tissue obtained from patients who died of COVID-19 in Wuhan, China. Strikingly, the viral burden was low in all samples, which suggests that the patient deaths may be related to the host response rather than an active fulminant infection. Examination of the colonic transcriptome of these patients suggested that SARS-CoV-2 impacted host responses even at a site with no obvious pathogenesis. Further proteomics analysis validated our transcriptome findings and identified several key proteins, such as the SARS-CoV-2 entry-associated protease cathepsins B and L and the inflammatory response modulator S100A8/A9, that are highly expressed in fatal cases, revealing potential drug targets for COVID-19.

A system biology approach for understanding the miRNA regulatory network in colon rectal cancer

2015 ◽  
Vol 11 (1) ◽  
pp. 1 ◽  
Author(s):  
Meeta Pradhan ◽  
Kshithija Nagulapalli ◽  
Lakenvia Ledford ◽  
Yogesh Pandit ◽  
Mathew Palakal
Keyword(s):  
Rectal Cancer ◽  
Regulatory Network ◽  
System Biology ◽  
System Biology Approach ◽  
Colon Rectal Cancer

scholarly journals A system biology approach highlights a hormonal enhancer effect on regulation of genes in a nitrate responsive "biomodule"

2009 ◽  
Vol 3 (1) ◽  
pp. 59 ◽  
Author(s):  
Damion Nero ◽  
Gabriel Krouk ◽  
Daniel Tranchina ◽  
Gloria M Coruzzi
Keyword(s):  
System Biology ◽  
System Biology Approach

Cardiovascular Disease-related Hospital Admissions of Patients with Inflammatory Arthritis

2014 ◽  
Vol 42 (2) ◽  
pp. 188-192
Author(s):  
Jennie Ursum ◽  
Mark M.J. Nielen ◽  
Jos W.R. Twisk ◽  
Mike J.L. Peters ◽  
François G. Schellevis ◽  
...  
Keyword(s):  
Primary Care ◽  
Hospital Admission ◽  
Inflammatory Arthritis ◽  
Hospital Admissions ◽  
High Rate ◽  
Hospital Data ◽  
Cvd Risk ◽  
Dutch Hospital ◽  
Services Research ◽  
Increased Risk

Objective.Patients with inflammatory arthritis (IA) have an increased risk of cardiovascular diseases (CVD), suggesting a high rate of CVD-related hospitalizations, but data on this topic are limited. Our study addressed hospital admissions for CVD in a primary care–based population of patients with IA and controls.Methods.All newly diagnosed patients with IA between 2001 and 2010 were selected from electronic medical records of the Netherlands Institute for Health Services Research Primary Care database, representing a national network of general practices. Two control patients matched for age, sex, and practice were selected for each patient with IA. Hospital admission data for all patients was retrieved from the Dutch Hospital Data.Results.There were 2615 patients with IA and 5555 controls included in our study. CVD-related hospital admissions were observed more frequently among patients with IA as compared with control patients: 48% versus 36% (p < 0.001) in a followup period of 4 years. Patients with IA were more often hospitalized because of ischemic heart disease (OR 1.7, 95% CI 1.2–2.2) and for day-care admission because of cerebrovascular disease (OR 2.2, 95% CI 1.0–4.9).Conclusion.Increased hospital admission rates confirm the higher CVD burden among patients with IA compared with controls, and underscore the need for proper CVD risk management in patients with IA.

scholarly journals Role of Flt4 in Skin Protection against UVB Radiation: A System Biology Approach

2020 ◽  
Vol 11 (Suppl 1) ◽  
pp. S30-S36
Author(s):  
Babak Arjmand ◽  
Mostafa Rezaei-Tavirani ◽  
Mohammadreza Razzaghi ◽  
Mohammad Rostami-Nejad ◽  
Mostafa Hamdieh ◽  
...  
Keyword(s):  
System Biology ◽  
System Biology Approach ◽  
Uvb Radiation ◽  
Skin Protection
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