Dissecting the cellular effects of SARS-CoV-2 components

  • Filchakova, Olena (PI)

Project: Monitored by Research Administration

Project Details

Grant Program

Faculty Development Competitive Research Grants Program 2022-2024

Project Description

Coronovirus disease 2019 (COVID-19) is a pandemic disease that emerged less than two years ago and already changed the lives of all people. The disease is caused by a novel virus, Severe Acute Respiratory Syndrome Coronovirus 2 (SARS-CoV-2) that belongs to family Coronaviridae, subfamily Orthocoronavirus, genus Betacoronavirus, subgenus Sarbecovirus. The virus is similar to SARS-CoV virus which caused SARS outbreak in 2002-2003 [1]. The virus is a positive-sense, single-stranded RNA virus, containing 29903 nucleotides. The viral genome contains a 5’-untranslated region (5’-UTR), ORF1ab coding for 16 nonstructural proteins and occupying two thirds of the genome, four structural genes including Spike surface glycoprotein gene (S gene), Envelope gene (E gene), Matrix gene (M gene), Nucleocapsid phosphoprotein gene (N gene), and several open reading frames with debatable annotations at the 3’- end [2]. Overall, viral genome codes for ~ 30 mature proteins. Function of some but not all protein product of the viral genome is characterized. For example, nonstructural proteins coded by ORF1a control genome, while nonstructural proteins coded by ORF1b are involved in replication. There is still much to learn regarding the functions and host-specific effect of viral proteins. The COVID-19 disease primarily affects respiratory system with variable symptoms ranging from mild cough to pneumonia [3]. Besides well-known effect on respiratory system, many reports suggest that SARS-CoV-2 virus is capable of targeting nervous system. First of all, many disease-affected people develop anosmia, while other suffer from different neurological symptoms [4,5]. Secondly, virus was detected within brain and cerebrospinal fluid in postmortem samples [6]. Lastly, the receptors with which virus gets access to the cell are present within neurons and glial cell [7]. The neurological problems observed in people affected by COVID-19 include anosmia, ageusia or dysgeusia, headache, stroke, seizure, and Guillain-Barre syndrome [8]. Anosmia is by far one of the most prominent symptoms suggesting involvement of nervous system in the COVID-19 pathogenesis [9]. Recent study by Meihardt et al. where post-mortem tissues were analyzed by quantitative real-time PCR (RTRqPCR) [10] demonstrated presence of viral RNA in olfactory mucosa in 20 out of 30 samples. This study suggests olfactory route used by virus to enter CNS. The cellular consequences of viral entry to the CNS as well as mechanism of cellular entry and types of affected cells are not well understood at the moment. There are multiple routes through which virus can gain an access to the cell, including neuronal and glial cell. The most well described route is through angiotensin-converting enzyme-2 (ACE-2) receptor [11]. However, there is very limited expression of ACE-2 within brain [12]. Recently proposed Neuropilin receptor is another possible entrance route for virus [13,14]. Besides this, there are suggestions that nicotinic acetylcholine receptors could play role in a viral cycle [15]. The cellular mechanisms triggered by viral entry into the neuronal cells are unknown but are crucial to understand. In the current proposal we are aiming at investigating the effect of protein components of SARS-CoV-2 virus on neurons and glial cells.
StatusActive
Effective start/end date1/1/2212/31/24

Keywords

  • SARS-CoV-2, nucleocapsid protein, glial cells, cytokines

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