SARS-CoV-2, More than a Respiratory Virus: Its Potential Role in Neuropathogenesis

Singal, Chitra Mohinder Singh; Jaiswal, Paritosh; Seth, Pankaj

doi:10.1021/acschemneuro.0c00251

Cited by 52 publications

(49 citation statements)

References 143 publications

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“…Thus, teleost fish models have been proposed as comparative models for human nasal infections and immunity [ 61 ]. Several viral pathogens infect the human host via the nasal epithelium including influenza virus [ 62 ] and SARS-CoV-2 [ 63 ]. Understanding innate immunity in the nasal mucosa is therefore critical for the effective design of immunoprophylactic strategies against respiratory and neurotropic viruses.…”

Section: Discussionmentioning

confidence: 99%

Vaccination Route Determines the Kinetics and Magnitude of Nasal Innate Immune Responses in Rainbow Trout (Oncorhynchus mykiss)

Dong

Tacchi

et al. 2020

Biology

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Many pathogens infect animal hosts via the nasal route. Thus, understanding how vaccination stimulates early nasal immune responses is critical for animal and human health. Vaccination is the most effective method to prevent disease outbreaks in farmed fish. Nasal vaccination induces strong innate and adaptive immune responses in rainbow trout and was shown to be highly effective against infectious hematopoietic necrosis (IHN). However, direct comparisons between intranasal, injection and immersion vaccination routes have not been conducted in any fish species. Moreover, whether injection or immersion routes induce nasal innate immune responses is unknown. The goal of this study is to compare the effects of three different vaccine delivery routes, including intranasal (IN), intramuscular (i.m.) injection and immersion (imm) routes on the trout nasal innate immune response. Expression analyses of 13 immune-related genes in trout nasopharynx-associated lymphoid tissue (NALT), detected significant changes in immune expression in all genes analyzed in response to the three vaccination routes. However, nasal vaccination induced the strongest and fastest changes in innate immune gene expression compared to the other two routes. Challenge experiments 7 days post-vaccination (dpv) show the highest survival rates in the IN- and imm-vaccinated groups. However, survival rates in the imm group were significantly lower than the IN- and i.m.-vaccinated groups 28 dpv. Our results confirm that nasal vaccination of rainbow trout with live attenuated IHNV is highly effective and that the protection conferred by immersion vaccination is transient. These results also demonstrate for the first time that immersion vaccines stimulate NALT immune responses in salmonids.

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Section: Discussionmentioning

confidence: 99%

Vaccination Route Determines the Kinetics and Magnitude of Nasal Innate Immune Responses in Rainbow Trout (Oncorhynchus mykiss)

Dong

Tacchi

et al. 2020

Biology

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“…Basically, the cytokine storm during the intrusion of SARS-CoV-2 may disrupt blood-brain barrier and may be associated with early progression of the aforementioned diseases 11 . Also, few cases of schizophrenia have also been noticed in post-COVID population 61 . Though the reasons for this increase in schizophrenia incidences are not clear.…”

Section: Sars-cov-2 and Its Impact On Neurodegenerative And Neuropsycmentioning

confidence: 99%

Understanding Structural Malleability of the SARS-CoV-2 Proteins and their Relation to the Comorbidities

Sen

Dey

Bandyopadhyay

et al. 2020

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of the coronavirus disease (CoVID-19), is a part of the β-coronaviridae family. In comparison with two other members of this family of coronaviruses infecting humans (SARS-CoV and Middle East Respiratory Syndrome (MERS) CoV), SARS-CoV-2 showed the most severe effects on the entire Earth population causing world-wide CoVID-19 pandemic. SARS-CoV-2 contains five major protein classes, such as four structural proteins (Nucleocapsid (N), Membrane (M), Envelop (E), and Spike Glycoprotein (S)) and Replicase polyproteins (R), which are synthesized as two polyproteins (ORF1a and ORF1ab) that are subsequently processed into 12 nonstructural proteins by three viral proteases. All these proteins share high sequence similarity with their SARS-CoV counterparts. Due to the severity of the current situation, most of the SARS-CoV-2-related research is focused on finding therapeutic solutions and the analysis of comorbidities during infection. However, studies on the peculiarities of the amino acid sequences of viral protein classes and their structure space analysis throughout the evolutionary time-frame are limited. At the same time, due to their structural malleability, viral proteins can be directly or indirectly associated with the dysfunctionality of the host cell proteins, which may lead to comorbidities during the infection and at the post infection stage. To fill these gaps, we conducted the evolutionary sequence-structure analysis of the viral protein classes to evaluate the rate of their evolutionary malleability. We also looked at the intrinsic disorder propensities of these viral proteins and confirmed that although they typically do not have long intrinsically disordered regions (IDRs), all of them have at least some levels of intrinsic disorder. Furthermore, short IDRs found in viral proteins are extremely effective and prioritize the proteins for host cell interactions, which may lead to host cell dysfunction. Next, the associations of viral proteins with the host cell proteins were studied, and a list of diseases which are associated with such host cell proteins was developed. Other than the usual set of diseases, we have identified some maladies, which may happen after the recovery from the infections. Comparison of the expression rates of the host cell proteins during the diseases suggested the existence of two distinct classes. First class includes proteins, which are directly associated with certain sets of diseases, where they have shared similar activities. Second class is related to the cytokine storm-mediated pro-inflammation (already known for its role in acute respiratory distress syndrome, ARDS), and neuroinflammation may trigger some of the neurological malignancies and neurodegenerative and neuropsychiatric diseases. Finally, since the transmembrane serine protease 2 (TMPRSS2), which is one of the leading proteins associated with the viral uptake, is an androgen-mediated protein, our study suggested that males and postmenopausal females can be more susceptible to the SARS-CoV-2 infection.

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“…Another factor that causes stroke in COVID-19 patients is venous and arterial thromboembolism. SARS-CoV-2 infection increases the blood thrombin levels and activation of coagulation factors and decreases anticoagulant levels by activating proinflammatory cytokines [23]. Another pathway causing CNS damage in SARS-CoV-2 infection is that antibodies produced against SARS-CoV-2 generate cerebral edema and autoimmune encephalitis by attacking the antigens in cerebral vessels or neurons [21].…”

Section: Effects Of Sars-cov-2 On Central Nervous Systemmentioning

confidence: 99%

“…Memantine and amantadine which are used for the treatment of Parkinson's disease, Alzheimer's disease and influenza have antiviral activity. Therefore, they can be effective for the prevention and treatment of viral replication in COVID-19-associated neuropathology [23].…”

Section: Covid-19 Dependent Neurological Damage Treatmentmentioning

confidence: 99%

What we know about COVID-19 and its treatment

Yakut¹,

Sakarcan²,

Şener³

2020

jrp

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Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) which is the human coronavirus and a member of the Coronaviridae family leads to fatal pneumonia cases. Severe acute respiratory syndrome corona virus 2 attaches to the cells in the human body through binding to the angiotensin converting enzyme 2 (ACE2) receptor with the spike (S) protein. Firstly, SARS-CoV-2 arised in China in late 2019 and was reported to the World Health Organization (WHO). The World Health Organization named the disease caused by this virus as corona virus disease (COVID)-19. SARS-CoV-2 which has human-to-human transmission through droplets, direct contact and aerosol routes have affected more than 10 million people and caused more than 500 thousand deaths. Clinical symptoms of COVID-19 are fever, dry cough, sore throat, respiratory distress, lung damage, and diarrhea. In severe cases, mechanical ventilation is required and multiple organ damage is encountered. COVID-19 is diagnosed with real-time polymerase chain reaction (PCR) technique which is applied to saliva and swab samples taken from the nose or nasal cavity. Lung damage is detected by computerized tomography (CT). COVID-19 develops more severely in patients with comorbidities such as hypertension, diabetes and cancer. While vaccine and drug development studies are continuing all over the world, available antiviral drugs such as umifenovir, remdesivir, favipiravir are also tested against SARS-CoV-2. Moreover, the plasma donated from the recovered patients are tested for COVID-19 treatment. Additionally, treating the inflammatory conditions developing due to COVID-19 and applying antimicrobial drugs against coinfections are among the current approaches.

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SARS-CoV-2, More than a Respiratory Virus: Its Potential Role in Neuropathogenesis

Cited by 52 publications

References 143 publications

Vaccination Route Determines the Kinetics and Magnitude of Nasal Innate Immune Responses in Rainbow Trout (Oncorhynchus mykiss)

Vaccination Route Determines the Kinetics and Magnitude of Nasal Innate Immune Responses in Rainbow Trout (Oncorhynchus mykiss)

Understanding Structural Malleability of the SARS-CoV-2 Proteins and their Relation to the Comorbidities

What we know about COVID-19 and its treatment

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