scholarly journals Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Joshua M. Thornbrough ◽  
Babal K. Jha ◽  
Boyd Yount ◽  
Stephen A. Goldstein ◽  
Yize Li ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Therapeutic Intervention ◽  
Middle East Respiratory Syndrome ◽  
Accessory Proteins ◽  
Rnase L ◽  
Human Coronavirus ◽  
Highly Pathogenic ◽  
Ns4b Protein

ABSTRACTMiddle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. Like many coronaviruses, MERS-CoV carries genes that encode multiple accessory proteins that are not required for replication of the genome but are likely involved in pathogenesis. Evasion of host innate immunity through interferon (IFN) antagonism is a critical component of viral pathogenesis. The IFN-inducible oligoadenylate synthetase (OAS)-RNase L pathway activates upon sensing of viral double-stranded RNA (dsRNA). Activated RNase L cleaves viral and host single-stranded RNA (ssRNA), which leads to translational arrest and subsequent cell death, preventing viral replication and spread. Here we report that MERS-CoV, a lineage CBetacoronavirus, and related bat CoV NS4b accessory proteins have phosphodiesterase (PDE) activity and antagonize OAS-RNase L by enzymatically degrading 2′,5′-oligoadenylate (2-5A), activators of RNase L. This is a novel function for NS4b, which has previously been reported to antagonize IFN signaling. NS4b proteins are distinct from lineage ABetacoronavirusPDEs and rotavirus gene-encoded PDEs, in having an amino-terminal nuclear localization signal (NLS) and are localized mostly to the nucleus. However, the expression level of cytoplasmic MERS-CoV NS4b protein is sufficient to prevent activation of RNase L. Finally, this is the first report of an RNase L antagonist expressed by a human or bat coronavirus and provides a specific mechanism by which this occurs. Our findings provide a potential mechanism for evasion of innate immunity by MERS-CoV while also identifying a potential target for therapeutic intervention.IMPORTANCEMiddle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (SARS-CoV). MERS-CoV, like other coronaviruses, carries genes that encode accessory proteins that antagonize the host antiviral response, often the type I interferon response, and contribute to virulence. We found that MERS-CoV NS4b and homologs from related lineage C bat betacoronaviruses BtCoV-SC2013 (SC2013) and BtCoV-HKU5 (HKU5) are members of the 2H-phosphoesterase (2H-PE) enzyme family with phosphodiesterase (PDE) activity. Like murine coronavirus NS2, a previously characterized PDE, MERS NS4b, can antagonize activation of the OAS-RNase L pathway, an interferon-induced potent antiviral activity. Furthermore, MERS-CoV mutants with deletion of genes encoding accessory proteins NS3 to NS5 or NS4b alone or inactivation of the PDE can activate RNase L during infection of Calu-3 cells. Our report may offer a potential target for therapeutic intervention if NS4b proves to be critical to pathogenesis inin vivomodels of MERS-CoV infection.

A Review of the Virology of SARS-CoV-2

2020 ◽  
Vol 7 (1) ◽  
pp. 69-77
Author(s):  
Aldonna Maria Susngi ◽  
◽  
Clara Ermine Sawian
Keyword(s):  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Causative Agent ◽  
Middle East Respiratory Syndrome ◽  
The Novel ◽  
Highly Pathogenic ◽  
Key Features

The novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19) is a β-coronavirus, which also includes the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome Coronavirus (MERS-CoV). Emerging in December 2019 from Wuhan, China, it has spread worldwide resulting in a pandemic that has not ended till date. This review highlights some of the key features of the virology of SARS-CoV-2.

scholarly journals CORONAVIRUS- A REVIEW

2021 ◽  
Vol 5 (6) ◽  
Author(s):  
Shilpa Jaryal ◽  
Gurpreet Kaur ◽  
Jageer Chhina ◽  
Jannat Sharma ◽  
Shreen Mann
Keyword(s):  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Respiratory Diseases ◽  
Middle East Respiratory Syndrome ◽  
Highly Pathogenic ◽  
Enveloped Viruses ◽  
The Family ◽  
Distinctive Morphology ◽  
Positive Sense ◽  
Corona Viruses

Coronavirus disease (COVID-19) is an infectious disease caused by a coronavirus. Coronaviruses are a group of enveloped viruses with nonsegmented, single-stranded, and positive-sense RNA genomes. Apart from infecting a variety of economically important vertebrates (such as pigs and chickens), six coronaviruses have been known to infect human hosts and cause respiratory diseases. Among them, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are zoonotic and highly pathogenic coronaviruses that have resulted in regional and global outbreaks Coronaviruses possess a distinctive morphology, the name being derived from the outer fringe, or corona‖ of embedded envelope protein. Members of the family Coronaviridae cause a broad spectrum of animal and human diseases. Uniquely, replication of the RNA genome proceeds through the generation of a nested set of viral mRNA molecules. Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Replication of HCoV is regulated by a diversity of host factors and induces drastic alterations in cellular structure and physiology. In this review all (as we possible) information about Corona viruses are given. Keywords: Corona virus, respiratory, viruses, Hcov, host, RNA.

scholarly journals Antagonism of dsRNA-Induced Innate Immune Pathways by NS4a and NS4b Accessory Proteins during MERS Coronavirus Infection

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Courtney E. Comar ◽  
Stephen A. Goldstein ◽  
Yize Li ◽  
Boyd Yount ◽  
Ralph S. Baric ◽  
...  
Keyword(s):  
Middle East ◽  
Respiratory Disease ◽  
Innate Immune ◽  
Middle East Respiratory Syndrome ◽  
Nuclear Localization Sequence ◽  
Accessory Proteins ◽  
Rnase L ◽  
Oligoadenylate Synthetase ◽  
Human Airway ◽  
Immune Pathways

ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in 2012 as a novel etiological agent of severe respiratory disease in humans. As during infection by other viruses, host sensing of viral double-stranded RNA (dsRNA) induces several antiviral pathways. These include interferon (IFN), oligoadenylate synthetase (OAS)-RNase L, and protein kinase R (PKR). Coronaviruses, including MERS-CoV, potently suppress the activation of these pathways, inducing only modest host responses. Our study describes the functions of two accessory proteins unique to MERS-CoV and related viruses, NS4a and NS4b, during infection in human airway epithelium-derived A549 cells. NS4a has been previously characterized as a dsRNA binding protein, while NS4b is a 2′,5′-phosphodiesterase with structural and enzymatic similarity to NS2 encoded by mouse hepatitis virus (MHV). We found that deletion of NS4a results in increased interferon lambda (IFNL1) expression, as does mutation of either the catalytic site or nuclear localization sequence of NS4b. All of the mutant viruses we tested exhibited slight decreases in replication. We previously reported that, like MHV NS2, NS4b antagonizes OAS-RNase L, but suppression of IFN is a previously unidentified function for viral phosphodiesterases. Unexpectedly, deletion of NS4a does not result in robust activation of the PKR or OAS-RNase L pathways. Therefore, MERS-CoV likely encodes other proteins that contribute to suppression or evasion of these antiviral innate immune pathways that should be an important focus of future work. This study provides additional insight into the complex interactions between MERS-CoV and the host immune response. IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) is the second novel zoonotic coronavirus to emerge in the 21st century and cause outbreaks of severe respiratory disease. More than 2,200 cases and 800 deaths have been reported to date, yet there are no licensed vaccines or treatments. Coronaviruses encode unique accessory proteins that are not required for replication but most likely play roles in immune antagonism and/or pathogenesis. Our study describes the functions of MERS-CoV accessory proteins NS4a and NS4b during infection of a human airway-derived cell line. Loss of these accessory proteins during MERS-CoV infection leads to host antiviral activation and modestly attenuates replication. In the case of both NS4a and NS4b, we have identified roles during infection not previously described, yet the lack of robust activation suggests much remains to be learned about the interactions between MERS-CoV and the infected host.

scholarly journals Human Coronavirus 229E Remains Infectious on Common Touch Surface Materials

mBio ◽  
2015 ◽  
Vol 6 (6) ◽  
Author(s):  
Sarah L. Warnes ◽  
Zoë R. Little ◽  
C. William Keevil
Keyword(s):  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Copper Alloy ◽  
Structural Damage ◽  
Respiratory Viruses ◽  
Middle East Respiratory Syndrome ◽  
Upper Respiratory Tract ◽  
Human Coronavirus ◽  
Surface Materials ◽  
Human Coronavirus 229E

ABSTRACTThe evolution of new and reemerging historic virulent strains of respiratory viruses from animal reservoirs is a significant threat to human health. Inefficient human-to-human transmission of zoonotic strains may initially limit the spread of transmission, but an infection may be contracted by touching contaminated surfaces. Enveloped viruses are often susceptible to environmental stresses, but the human coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have recently caused increasing concern of contact transmission during outbreaks. We report here that pathogenic human coronavirus 229E remained infectious in a human lung cell culture model following at least 5 days of persistence on a range of common nonbiocidal surface materials, including polytetrafluoroethylene (Teflon; PTFE), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. We have shown previously that noroviruses are destroyed on copper alloy surfaces. In this new study, human coronavirus 229E was rapidly inactivated on a range of copper alloys (within a few minutes for simulated fingertip contamination) and Cu/Zn brasses were very effective at lower copper concentration. Exposure to copper destroyed the viral genomes and irreversibly affected virus morphology, including disintegration of envelope and dispersal of surface spikes. Cu(I) and Cu(II) moieties were responsible for the inactivation, which was enhanced by reactive oxygen species generation on alloy surfaces, resulting in even faster inactivation than was seen with nonenveloped viruses on copper. Consequently, copper alloy surfaces could be employed in communal areas and at any mass gatherings to help reduce transmission of respiratory viruses from contaminated surfaces and protect the public health.IMPORTANCERespiratory viruses are responsible for more deaths globally than any other infectious agent. Animal coronaviruses that “host jump” to humans result in severe infections with high mortality, such as severe acute respiratory syndrome (SARS) and, more recently, Middle East respiratory syndrome (MERS). We show here that a closely related human coronavirus, 229E, which causes upper respiratory tract infection in healthy individuals and serious disease in patients with comorbidities, remained infectious on surface materials common to public and domestic areas for several days. The low infectious dose means that this is a significant infection risk to anyone touching a contaminated surface. However, rapid inactivation, irreversible destruction of viral RNA, and massive structural damage were observed in coronavirus exposed to copper and copper alloy surfaces. Incorporation of copper alloy surfaces in conjunction with effective cleaning regimens and good clinical practice could help to control transmission of respiratory coronaviruses, including MERS and SARS.

scholarly journals COVID-19 an Updated Roadmap – Current Scenario and Recent Development

2020 ◽  
Vol 13 (3) ◽  
pp. 283-287
Author(s):  
J. Yamuna ◽  
C. Sownthariya ◽  
S N Khadatkar
Keyword(s):  
Risk Factor ◽  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Systemic Infection ◽  
Middle East Respiratory Syndrome ◽  
Research Interest ◽  
Highly Pathogenic ◽  
Infected People ◽  
Current Scenario ◽  
Screening And Prevention

Coronavirus (COVID-19) is associated with human-to-human transmission. And it causes severe respiratory and systemic infection. Research interest on coronaviruses has been increased after the outbreak of the highly pathogenic Severe Acute respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Wuhan, China was first infected country for COVID-19 and it is now spread wordwide. As on April 14 there are more than 100,000 death reported all over the country. The animal to human transmission is suspected to be the route cause of the viruses. Further investigation need to be confirmed for the origin of the noval virus. COVID-19 was recently identified in saliva of infected people. So the potential transmission of the virus is through saliva of infected people. In this article, we discuss the roadmap of COVID-19 and summerised the clinical clarification, diagnosis, causes and risk factor, currently available test, screening and prevention.

scholarly journals Passive Immunity for Coronavirus Disease 2019: A Commentary on Therapeutic Aspects Including Convalescent Plasma

2020 ◽  
Vol 46 (07) ◽  
pp. 796-803 ◽  
Author(s):  
Paul F. Lindholm ◽  
Glenn Ramsey ◽  
Hau C. Kwaan
Keyword(s):  
Innate Immunity ◽  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibodies ◽  
Immunoglobulin M ◽  
Middle East Respiratory Syndrome ◽  
Treatment Modalities ◽  
Passive Immunity ◽  
Effective Vaccine ◽  
Severe Illness

AbstractIn the ongoing pandemic of coronavirus disease 2019 (COVID-19), the novel virus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is infecting a naïve population. The innate immunity of the infected patient is unable to mount an effective defense, resulting in a severe illness with substantial morbidity and mortality. As most treatment modalities including antivirals and anti-inflammatory agents are mostly ineffective, an immunological approach is needed. The mechanism of innate immunity to this viral illness is not fully understood. Passive immunity becomes an important avenue for the management of these patients. In this article, the immune responses of COVID-19 patients are reviewed. As SARS-CoV-2 has many characteristics in common with two other viruses, SARS-CoV that cause severe acute respiratory syndrome (SARS) and MERS-CoV (Middle East respiratory syndrome coronavirus) that causes Middle East respiratory syndrome (MERS), the experiences learned from the use of passive immunity in treatment can be applied to COVID-19. The immune response includes the appearance of immunoglobulin M followed by immunoglobulin G and neutralizing antibodies. Convalescent plasma obtained from patients recovered from the illness with high titers of neutralizing antibodies was successful in treating many COVID-19 patients. The factors that determine responses as compared with those seen in SARS and MERS are also reviewed. As there are no approved vaccines against all three viruses, it remains a challenge in the ongoing development for an effective vaccine for COVID-19.

scholarly journals Does the novel coronavirus 2019 like heart more than the other family members of coronaviruses?

2020 ◽  
Vol 12 (2) ◽  
pp. 156-157
Author(s):  
Mohammad Mostafa Ansari Ramandi ◽  
Mohammadreza Baay ◽  
Nasim Naderi
Keyword(s):  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Family Members ◽  
Middle East Respiratory Syndrome ◽  
The Other ◽  
The Novel ◽  
The World ◽  
Future Challenges ◽  
Novel Coronavirus ◽  
Coronavirus Infections

The disaster due to the novel coronavirus disease 2019 (COVID-19) around the world has made investigators enthusiastic about working on different aspects of COVID-19. However, although the pandemic of COVID-19 has not yet ended, it seems that COVID-19 compared to the other coronavirus infections (the Middle East Respiratory Syndrome [MERS] and Severe Acute Respiratory Syndrome [SARS]) is more likely to target the heart. Comparing the previous presentations of the coronavirus family and the recent cardiovascular manifestations of COVID-19 can also help in predicting possible future challenges and taking measures to tackle these issues.

scholarly journals Penanggulangan Virus Covid – 19 melalui Penyaluran Handsanitizer dan Sabun Cuci Tangan Alami serta Penyemprotan Disenfektan di desa Ngale, Kecamatan Pilangkenceng, Kabupaten Madiun

Batoboh ◽  
2021 ◽  
Vol 6 (1) ◽  
pp. 10
Author(s):  
Reza Kusuma Setyansah
Keyword(s):  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Middle East Respiratory Syndrome ◽  
Sars Coronavirus

Coronavirus merupakan keluarga besar virus yang menyebabkan penyakit pada manusia, biasanya menyebabkan penyakit infeksi saluran pernapasan, mulai flu biasa hingga penyakit yang serius seperti Middle East Respiratory Syndrome (MERS) dan Sindrom Pernafasan Akut Berat/ Severe Acute Respiratory Syndrome (SARS). Coronavirus jenis baru yang ditemukan pada manusia sejak kejadian luar biasa muncul di Wuhan Cina, pada Desember 2019, kemudian diberi nama Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV2), dan menyebabkan penyakit Coronavirus Disease-2019 (COVID-19). Salah satu cara gampang melakukan pencegahan terhadap penyebaran virus ini adalah dengan menggunakan Handsanitizer alami. Menurut Organisasi Kesehatan Dunia (WHO), Handsanitizer alami harus mengandung setidaknya 60% alkohol untuk bekerja secara efektif. Selain handsanitizer, dengan melalukan metode penyemprotan disenfektan menggunakan cairan disenfektan. Disenfektan merupakan bahan kimia yang berguna untuk mencegah pertumbuhan bakteri ataupun jasad renik pada permukaan benda mati. Pelaksanaan pengabdian kepada masyarakat mengadakan penyaluran handsanitizer dan sabun cuci tangan alami serta penyemprotan disenfektan di desa Ngale sebagai upaya pencegahan Covid-19. Metode dalam pelaksanaan kegiatan ini yaitu wawancara dan diskusi bersama kepala desa Ngale. Kegiatan ini diharapkan mampu menumbuhkan kesadaran pada masyarakat akan pentingnya menjaga kebersihan, salah satunya menjaga kebersihan tangan serta dapat memutus mata rantai penyebaran Covid-19 di desa Ngale Kec Pilangkenceng Kab Madiun.

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