Neurotropism of SARS-CoV-2 and its neuropathological alterations: Similarities with other coronaviruses

Hu, Jingman; Jolkkonen, Jukka; Zhao, Chuansheng

doi:10.1016/j.neubiorev.2020.10.012

Cited by 61 publications

(70 citation statements)

References 184 publications

(273 reference statements)

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“…Homology to human mitochondrial proteins may enable viral proteins to bind to and manipulate mitochondrial protein function to promote viral entry and modulate host responses to viral infection (29). The enrichment of gene ontology terms associated with neurological processes in consistent with the neuroinvasive potential of SARS-CoV-2 (30,31,32). Patients with COVID-19 show signs of neurologic involvement including headache, loss of taste and smell, or, less frequently, encephalopathy and acute cerebrovascular disease (33,34).…”

Section: Discussionmentioning

confidence: 93%

A systems-based method to repurpose marketed therapeutics for antiviral use: a SARS-CoV-2 case study

Wang¹,

Withers²,

Ricchiuto³

et al. 2021

Life Sci. Alliance

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This study describes two complementary methods that use network-based and sequence similarity tools to identify drug repurposing opportunities predicted to modulate viral proteins. This approach could be rapidly adapted to new and emerging viruses. The first method built and studied a virus–host–physical interaction network; a three-layer multimodal network of drug target proteins, human protein–protein interactions, and viral–host protein–protein interactions. The second method evaluated sequence similarity between viral proteins and other proteins, visualized by constructing a virus–host–similarity interaction network. Methods were validated on the human immunodeficiency virus, hepatitis B, hepatitis C, and human papillomavirus, then deployed on SARS-CoV-2. Comparison of virus–host–physical interaction predictions to known antiviral drugs had AUCs of 0.69, 0.59, 0.78, and 0.67, respectively, reflecting that the scores are predictive of effective drugs. For SARS-CoV-2, 569 candidate drugs were predicted, of which 37 had been included in clinical trials for SARS-CoV-2 (AUC = 0.75, P-value 3.21 × 10−3). As further validation, top-ranked candidate antiviral drugs were analyzed for binding to protein targets in silico; binding scores generated by BindScope indicated a 70% success rate.

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Section: Discussionmentioning

confidence: 93%

A systems-based method to repurpose marketed therapeutics for antiviral use: a SARS-CoV-2 case study

Wang¹,

Withers²,

Ricchiuto³

et al. 2021

Life Sci. Alliance

View full text Add to dashboard Cite

show abstract

“…This evidence led some authors to suggest that SARS-CoV-2 could infect brainstem neurons by crossing the blood-brain barrier (BBB) [31] , [43] , [47] . Alternately, SARS-CoV-2 could hijack macrophages, which also express ACE2 [48] , to cross the BBB and to access the brain [47] , [49] , as demonstrated for human immunodeficiency virus (HIV) [50] , or it could infect the choroid plexus [47] , [51] , thereby disrupting the blood-cerebrospinal fluid barrier.…”

Section: Neurotropism Of Sars-cov-2 Short-circuits the Neural Cardiovmentioning

confidence: 99%

Understanding the heart-brain axis response in COVID-19 patients: A suggestive perspective for therapeutic development

Lionetti

Coppini

Gerbino

et al. 2021

Pharmacological Research

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In-depth characterization of heart-brain communication in critically ill patients with severe acute respiratory failure is attracting significant interest in the COronaVIrus Disease 19 (COVID-19) pandemic era during intensive care unit (ICU) stay and after ICU or hospital discharge. Emerging research has provided new insights into pathogenic role of the deregulation of the heart-brain axis (HBA), a bidirectional flow of information, in leading to severe multiorgan disease syndrome (MODS) in patients with confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Noteworthy, HBA dysfunction may worsen the outcome of the COVID-19 patients. In this review, we discuss the critical role HBA plays in both promoting and limiting MODS in COVID-19. We also highlight the role of HBA as new target for novel therapeutic strategies in COVID-19 in order to open new translational frontiers of care. This is a translational perspective from the Italian Society of Cardiovascular Researches.

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“…IL-10 has been shown to be able to both augment cellular cytotoxicity against MHV infected cells through IFN-γ, improving outcome, and to protect from neuronal damage by dampening the adaptive immune response, concurrently, promoting chronic infection including neurotrophic coronavirus encephalomyelitis ( 99 ). Notably, SARS-CoV-2 is also neurotropic ( 100 ), but severity of neuropathology does not appear to correlate with presence of the virus in the CNS and may rather be mediated by neuroinflammation in the brainstem ( 101 ).…”

Section: Ambiguous Role Of Il-10 In Lung Injury and Infectionmentioning

confidence: 99%

Lung Protection vs. Infection Resolution: Interleukin 10 Suspected of Double-Dealing in COVID-19

et al. 2021

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The pathological processes by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that make the virus a major threat to global health are insufficiently understood. Inefficient viral clearance at any stage is a hallmark of coronavirus disease 2019 (COVID-19). Disease severity is associated with increases in peripheral blood cytokines among which interleukin 10 (IL-10) increases particularly early and independent of patient age, which is not seen in active SARS-CoV infection. Here, we consider the known multi-faceted immune regulatory role of IL-10, both in protecting the lung from injury and in defense against infections, as well as its potential cellular source. While the absence of an IL-10 response in SARS is thought to contribute to early deterioration, we suspect IL-10 to protect the lung from early immune-mediated damage and to interfere with viral clearance in COVID-19. This may further both viral spread and poor outcome in many high-risk patients. Identifying the features of the viral genotype, which specifically underlie the different IL-10 dynamics as an etiological endotype and the different viral load kinetics and outcomes as clinical phenotype, may unveil a new immune evasive strategy of SARS-CoV-2.

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Neurotropism of SARS-CoV-2 and its neuropathological alterations: Similarities with other coronaviruses

Abstract: Highlights Neurologic manifestations are seen among patients with COVID-19. COVID-19 may attack the brain through hematogenous route or neuronal dissemination. Neuronal damage is caused either by direct virus effects or by immunopathology.

Cited by 61 publications

References 184 publications

A systems-based method to repurpose marketed therapeutics for antiviral use: a SARS-CoV-2 case study

A systems-based method to repurpose marketed therapeutics for antiviral use: a SARS-CoV-2 case study

Understanding the heart-brain axis response in COVID-19 patients: A suggestive perspective for therapeutic development

Lung Protection vs. Infection Resolution: Interleukin 10 Suspected of Double-Dealing in COVID-19

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