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INTERNET | Internet Software & Services / Email
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Founded Year

2012

Stage

Debt | Alive

Total Raised

$3.03M

About Vero

Vero offers an email platform that automates workflows, has real time event tracking and segmentation of all data.

Vero Headquarter Location

Sydney, New South Wales,

Australia

650-643-9866

Latest Vero News

Study shows SARS-CoV-2 prompts NLRP3 inflammasome activation through spike-ACE2 receptor interaction

Jan 17, 2022

Neuroinflammation – a hallmark of neurodegenerative diseases, can be driven by a variety of triggers within the central nervous system (CNS). Such stimuli may include – pathogens, injury, toxic metabolites, and protein aggregates. Among pathogens, viruses may also accelerate neurodegeneration, and this concept is gaining attention in the current coronavirus disease 2019 (COVID-19) pandemic. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to invade the brain. Evidence suggests that SARS-CoV-2 patients exhibit signs of viral invasions in multiple organs, along with extensive microglial activation and pronounced neuroinflammation in the brainstem. The study The aim of a new study published in bioRxiv * preprint server was to assess the NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in response to SARS-CoV-2 and its spike protein , and the effects of this exposure in the presence of a-synuclein protein aggregate fibrils. Here, human monocyte-derived microglia (MDMi) cellular model was used, following an established protocol to obtain adult microglia. Findings The findings showed that SARS-CoV-2 isolates and even spike protein alone can prime and activate the NLRP3 inflammasome in human microglia through nuclear factor kappa B (NF-κB) and angiotensin-converting enzyme 2 (ACE2). Additionally, microglia exposed to SARS-CoV-2 or its spike protein potentiated a-synuclein mediated NLRP3 activation – indicating a possible mechanism for COVID-19 for precipitating movement disorders in some infected individuals. The MDMi cellular model showed no secreted virus in the supernatant of infected MDMi and mouse primary microglia (mMi) cell culture supernatants. These contrasted with that in Vero E6 and Caco2 cells. Hence, microglia cells did not seem to allow SARS-CoV-2 replication in vitro. MDMi expressed ACE2 mRNA, yet, at lower levels than that of Vero E6 and Caco2 cells. Western blot analysis revealed that ACE2 protein levels varied greatly in individual donors and elicited a differential pattern of expression than those of Vero E6 and Caco2 cells. The latter Related Stories The control cells (VeroE6 and Caco2) displayed an expected full-length size of the glycosylated ACE2 form of approximately 120 KDa, while microglia cells showed molecular weights of ~135 and ~100 kDa. Notably, similar patterns have been also found in endothelial cells and heart tissue from COVID-19 patients. Viral binding to MDMi was evident. Higher levels of intracellular luciferase activity were found in microglia cells infected with the pseudo-virus compared to the non- glycoprotein control (NE). The results suggested that SARS-CoV-2 was capable of invading human microglia cells. A high level of ZsGreen fluorescent protein expression was observed in Vero E6 cells whereas, no intracellular ZsGreen fluorescence was noted in MDMi. Thus, the virus could not establish replication in these cells. It was also noted that even in the absence of priming, SARS-CoV-2 exposure can directly activate the inflammasome in MDMi. In fact, the virus could both prime and activate the inflammasome. In addition, even the spike protein was capable of both, priming and activating the inflammasome and could itself initiate inflammasome activation directly in human microglia. The spike protein was found to activate NLRP3 in human microglia-like cells through the ACE2 receptor. The vigorous virus-mediated inflammasome activation, in vivo, can be explained through the inflammasome activation by SARS-CoV-2 in MDMi without the need for priming. Furthermore, the viral spike protein could induce innate immune responses through NF-kB signaling. Parkinsonism cases have been recorded after SARS-CoV-2 infection, which could have occurred due to an increased proinflammatory environment—precipitated by the blood-brain barrier (BBB) disruption, peripheral cell infiltration and microglial activation. Aging, poor health and ongoing synucleinopathies may enhance such complications, accelerate neuronal loss and increase the susceptibility to developing Parkinson’s disease (PD) post-SARS-CoV-2 infection. Previous evidence has shown deterioration of motor performance and motor-related disability is seen in PD patients recovering from COVID-19. Animal studies have revealed Lewy body formation in the brains of SARS-CoV-2 infected macaques. The results illustrate the molecular mechanisms of SARS-CoV-2 that cause the activation of microglia and lead to neurological manifestations. It was stated that spike protein-mediated priming and activation of microglia through the ACE2-NF499 kB axis may promote NLRP3 inflammasome activation leading to neuroinflammation and neurological phenotypes. However, this adverse effect could be amplified in the background of neurodegenerative disease, such as PD. *Important notice bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information. Journal reference: Albornoz, E., Amarilla, A., Modhiran, N., et al. (2022). SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through spike-ACE2 receptor interaction. bioRxiv. doi: 10.1101/2022.01.11.475947 https://www.biorxiv.org/content/10.1101/2022.01.11.475947v1

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Vero Patents

Vero has filed 4 patents.

The 3 most popular patent topics include:

  • Banking technology
  • Bottles
  • Domestic implements
patents chart

Application Date

Grant Date

Title

Related Topics

Status

7/11/2019

3/2/2021

Bottles, Food packaging, Food storage containers, Domestic implements, Seals (mechanical)

Grant

Application Date

7/11/2019

Grant Date

3/2/2021

Title

Related Topics

Bottles, Food packaging, Food storage containers, Domestic implements, Seals (mechanical)

Status

Grant

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