Master Regulator Analysis of the SARS-CoV-2/Human interactome

Guzzi, Pietro Hiram; Mercatelli, Daniele; Ceraolo, Carmine; Giorgi, Federico M.

doi:10.1101/2020.03.15.992925

Cited by 103 publications

(124 citation statements)

References 78 publications

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“…Intriguingly, EEF1A1, a target of several viruses, is known to be activated upon inflammation 62 . This CSP is independently identified as one of the major regulators in human-SARS-CoV-2 predicted interactome 63 . The CSPs, which regulate protein folding and translation, for example EIAF1, could be utilized by SARS-CoV-2 to halt host protein translation, folding and protein quality control.…”

Section: Discussionmentioning

confidence: 97%

Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis

Kumar

Mishra

Mehmood

et al. 2020

Preprint

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COVID-19 (Coronavirus disease 2019) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the pathophysiology of this deadly virus is complex and largely unknown, we employ a network biology-fueled approach and integrated multiomics data pertaining to lung epithelial cells-specific coexpression network and human interactome to generate Calu-3-specific human-SARS-CoV-2 Interactome (CSI). Topological clustering and pathway enrichment analysis show that SARS-CoV-2 target central nodes of host-viral network that participate in core functional pathways. Network centrality analyses discover 28 high-value SARS-CoV-2 targets, which are possibly involved in viral entry, proliferation and survival to establish infection and facilitate disease progression. Our probabilistic modeling framework elucidates critical regulatory circuitry and molecular events pertinent to COVID-19, particularly the host modifying responses and cytokine storm. Overall, our network centric analyses reveal novel molecular components, uncover structural and functional modules, and provide molecular insights into SARS-CoV-2 pathogenicity.

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Section: Discussionmentioning

confidence: 97%

Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis

Kumar

Mishra

Mehmood

et al. 2020

Preprint

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“…These findings suggest possible mechanisms through which CoV-2 infection could lead to anosmia or other forms of olfactory dysfunction. 14,15,17,19,49,52…”

Section: Diagnosis Of Smell and Taste Lossmentioning

confidence: 99%

“…2019-nCoV effectively uses angiotensin converting enzyme 2 receptor (ACE2) as a receptor for cell invasion. [13][14][15][16][17][18][19] The current knowledge on SARS-CoV-2 is relative scarce, and most of it comes from deductions than actual data analysis. 3,[20][21][22][23] Coronaviruses are known as enveloped viruses with a positive-sense single-stranded RNA genome, and their helical symmetry nucleocapsid is about 26-32 kilobases in size, making it the largest investigated genome among RNA viruses.…”

mentioning

confidence: 99%

<strong></strong><strong>Anosmia and Ageusia as Initial or Unique Symptoms after SARS-COV-2 Virus Infection</strong>

Machado¹,

Gutierrez²

2020

Preprint

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SARS-CoV-2 (CoV-2) is a coronavirus which is causing the actual COVID-19 pandemic. The disease caused by 2019 new coronavirus (2019-nCoV) was named coronavirus disease-19 (COVID-19) by the World Health Organization in February 2020. Primary non-specific reported symptoms of 2019-nCoV infection at the prodromal phase are malaise, fever, and dry cough. The most commonly reported signs and symptoms are fever (98%), cough (76%), dyspnea (55%), and myalgia or fatigue (44%). Nonetheless, recent reports suggest an association between COVID-19 and altered olfactory and taste functions, although smell seems to be more affected than taste. These associations of smell and taste dysfunctions and CoV-2 are consistent with case reports describing a patient with SARS with long term anosmia after recovery from respiratory distress, with the observation that olfactory function is commonly altered after infection with endemic coronaviruses, and with data demonstrating that intentional experimental infection of humans with CoV-299 raises the thresholds at which odors can be detected. Post-viral anosmia and is one of the leading causes of loss of sense of smell in adults, accounting for up to 40% cases of anosmia. Viruses that give rise to the common cold are well known to cause post-infectious loss, and over 200 different viruses are known to cause upper respiratory tract infections. I reviewed the possible mechanisms of smell and taste loss in COVID-19. I concluded that since the existence of such a relationship is likely, it is highly recommended that those patients who experience complications such as smell and/or taste loss, even as unique symptoms, should be considered as potential SARS-CoV-2 virus carriers.

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“…ACE2 is expressed in several tissues, including airway epithelia, small intestine, heart, kidney, lung, testis and brain [2,3]. Concerning the function of ACE2, it takes part in the Renin Angiotensin System (RAS), by converting the Ang I to Ang- (1)(2)(3)(4)(5)(6)(7)(8)(9) and Ang II to Ang-(1-7) peptides, respectively. The function of Ang-(1-9) peptide is still unknown, whereas Ang-(1-7) peptide act as a vasodilator.…”

Section: Introductionmentioning

confidence: 99%

Analysis of ACE2 Genetic Variability Among Populations Highlights A Possible Link With COVID19-Related Neurological Complications

Strafella

Caputo

Termine

et al. 2020

Preprint

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The Angiotensin-converting enzyme 2 (ACE2) has been recently recognized as the entry receptor of the novel pathogenic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2). The presence of structural and sequence variants in ACE2 gene may affect its expression in different tissues and determine a differential response to SARS-Cov-2 infection and COVID19-related phenotype. The present study investigated the genetic variability of ACE2 in terms of Single Nucleotide Variants (SNVs), Copy Number Variations (CNVs) and expression Quantitative Loci (eQTLs) in a cohort of 268 individuals representative of the Italian general population. The analysis identified 5 SNVs (rs35803318, rs41303171, rs774469453, rs773676270, rs2285666) which displayed a significantly different frequency distribution in the Italian cohort compared to the worldwide populations. The analysis of eQTLs located in and targeting ACE2, revealed a high distribution of eQTL variants in different brain tissues, suggesting a possible link between the genetic variability of ACE2 and the neurological complications in patients with COVID19. Further research is needed to clarify the possible relationship between ACE2 expression and the susceptibility to neurological complications in patients with COVID19. In fact, patients at higher risk of neurological involvement may need different monitoring and treatment strategies in order to prevent severe, permanent brain injury.

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Master Regulator Analysis of the SARS-CoV-2/Human interactome

Cited by 103 publications

References 78 publications

Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis

Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis

<strong></strong><strong>Anosmia and Ageusia as Initial or Unique Symptoms after SARS-COV-2 Virus Infection</strong>

Analysis of ACE2 Genetic Variability Among Populations Highlights A Possible Link With COVID19-Related Neurological Complications

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