scholarly journals Protein Intrinsic Disorder and Evolvability of MERS-CoV

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 608
Author(s):  
Vladimir N. Uversky ◽  
Elrashdy M. Redwan ◽  
Abdullah A. Aljadawi

Middle East Respiratory Syndrome (MERS) is a viral respiratory disease caused by one of the human coronaviruses, MERS-CoV [...]

2020 ◽  
Vol 2 (1) ◽  
pp. 43
Author(s):  
Heru Wijono

Abstract— Covid -19, a virus strain and a member of family with known member as Severe Acute Respiratory Disease (SARS) or Middle East Respiratory Syndrome (MERS), but having a potentially lethal differences in not readily recognized by our immunity. Classified as betacoronavirus, with incubation period up to 14 days, the sign and symptoms can be highly variable, from asymptomatic to mild to criticalin the form of severe pneumonia. Almost half the persons infected did not show any symptoms, but in cases of people with comorbidities such as advanced age, pregnancy, obesity or other certain diseases, could increase the likelihood of morbidity and even potentially fatal. Covid-19 has spread globally, including Indonesia, with a potentially increased number of cases, prevention in covid-19 protocol is a necessity. Keywords: Covid-19, SARS, symptoms, variable, prevention Abstrak— Covid-19, yang sebelumnya dikenal sebagai virus strain dari kelompok family yang sama dengan Severe Acute Respiratory Disease (SARS) atau Middle East Respiratory Syndrome (MERS), tapi memiliki fatalitas yang secara potensial lebih tinggi, karena bersiafat novel bagi sistem imunitas kita. Termasuk betacoronavirus, dengan masa inkubasi sampai dengan 14 hari, tanda dan gejala penyakit bisa sangat bervariasi, mulai dari asimtomatik, ringan sampai berat, dalam bentuk pneumonia berat. Hamper separuh penderita yang terinfeksi tidak menunjukkan gejala sama sekali, tapi pada penderita dengan komorbiditas seperti usia lanjut, kehamilan, obesitas atau penyakit kronis tertentu, resiko moribiditas dan mortalitas dapat meningkat. Covid-19 saat ini sudah menyebar ke seluruh dunia, termasuk Indonesia, dengan adanya potensi kenaikan kasus lebih banyak, pencegahan dalam bentuk protocol covid-19 bersifat mutlak diperlukan. Kata kunci: Covid-19, SARS, gejala, bervariasi, pencegahan


Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 396 ◽  
Author(s):  
Alice N. Kiyong’a ◽  
Elizabeth A. J. Cook ◽  
Nisreen M. A. Okba ◽  
Velma Kivali ◽  
Chantal Reusken ◽  
...  

Middle East respiratory syndrome (MERS) is a respiratory disease caused by a zoonotic coronavirus (MERS-CoV). Camel handlers, including slaughterhouse workers and herders, are at risk of acquiring MERS-CoV infections. However, there is limited evidence of infections among camel handlers in Africa. The purpose of this study was to determine the presence of antibodies to MERS-CoV in high-risk groups in Kenya. Sera collected from 93 camel handlers, 58 slaughterhouse workers and 35 camel herders, were screened for MERS-CoV antibodies using ELISA and PRNT. We found four seropositive slaughterhouse workers by PRNT. Risk factors amongst the slaughterhouse workers included being the slaughterman (the person who cuts the throat of the camel) and drinking camel blood. Further research is required to understand the epidemiology of MERS-CoV in Africa in relation to occupational risk, with a need for additional studies on the transmission of MERS-CoV from dromedary camels to humans, seroprevalence and associated risk factors.


2015 ◽  
Vol 89 (7) ◽  
pp. 3859-3869 ◽  
Author(s):  
Vivian A. Scheuplein ◽  
Janna Seifried ◽  
Anna H. Malczyk ◽  
Lilija Miller ◽  
Lena Höcker ◽  
...  

ABSTRACTThe Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as the causative agent of a severe respiratory disease with a fatality rate of approximately 30%. The high virulence and mortality rate prompted us to analyze aspects of MERS-CoV pathogenesis, especially its interaction with innate immune cells such as antigen-presenting cells (APCs). Particularly, we analyzed secretion of type I and type III interferons (IFNs) by APCs, i.e., B cells, macrophages, monocyte-derived/myeloid dendritic cells (MDDCs/mDCs), and by plasmacytoid dendritic cells (pDCs) of human and murine origin after inoculation with MERS-CoV. Production of large amounts of type I and III IFNs was induced exclusively in human pDCs, which were significantly higher than IFN induction by severe acute respiratory syndrome (SARS)-CoV. Of note, IFNs were secreted in the absence of productive replication. However, receptor binding, endosomal uptake, and probably signaling via Toll-like receptor 7 (TLR7) were critical for sensing of MERS-CoV by pDCs. Furthermore, active transcription of MERS-CoV N RNA and subsequent N protein expression were evident in infected pDCs, indicating abortive infection. Taken together, our results point toward dipeptidyl peptidase 4 (DPP4)-dependent endosomal uptake and subsequent infection of human pDCs by MERS-CoV. However, the replication cycle is stopped after early gene expression. In parallel, human pDCs are potent IFN-producing cells upon MERS-CoV infection. Knowledge of such IFN responses supports our understanding of MERS-CoV pathogenesis and is critical for the choice of treatment options.IMPORTANCEMERS-CoV causes a severe respiratory disease with high fatality rates in human patients. Recently, confirmed human cases have increased dramatically in both number and geographic distribution. Understanding the pathogenesis of this highly pathogenic CoV is crucial for developing successful treatment strategies. This study elucidates the interaction of MERS-CoV with APCs and pDCs, particularly the induction of type I and III IFN secretion. Human pDCs are the immune cell population sensing MERS-CoV but secrete significantly larger amounts of IFNs, especially IFN-α, than in response to SARS-CoV. A model for molecular virus-host interactions is presented outlining IFN induction in pDCs. The massive IFN secretion upon contact suggests a critical role of this mechanism for the high degree of immune activation observed during MERS-CoV infection.


2015 ◽  
Vol 468 (2) ◽  
pp. 215-226 ◽  
Author(s):  
Miklós Békés ◽  
Wioletta Rut ◽  
Paulina Kasperkiewicz ◽  
Monique P.C. Mulder ◽  
Huib Ovaa ◽  
...  

We compare processing proteases from two human coronaviruses - the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) hCoVs - with respect to their activities and substrate specificities for ubiquitin (Ub)-like signaling molecules, Ub and ISG15 (interferon stimulated gene 15); and doing so, we uncover a unique mode of polyUb recognition by the SARS protease.


2016 ◽  
Vol 91 (5) ◽  
Author(s):  
Stephen A. Goldstein ◽  
Joshua M. Thornbrough ◽  
Rong Zhang ◽  
Babal K. Jha ◽  
Yize Li ◽  
...  

ABSTRACT Viruses in the family Coronaviridae, within the order Nidovirales, are etiologic agents of a range of human and animal diseases, including both mild and severe respiratory diseases in humans. These viruses encode conserved replicase and structural proteins as well as more diverse accessory proteins, encoded in the 3′ ends of their genomes, that often act as host cell antagonists. We previously showed that 2′,5′-phosphodiesterases (2′,5′-PDEs) encoded by the prototypical Betacoronavirus, mouse hepatitis virus (MHV), and by Middle East respiratory syndrome-associated coronavirus antagonize the oligoadenylate-RNase L (OAS-RNase L) pathway. Here we report that additional coronavirus superfamily members, including lineage A betacoronaviruses and toroviruses infecting both humans and animals, encode 2′,5′-PDEs capable of antagonizing RNase L. We used a chimeric MHV system (MHVMut) in which exogenous PDEs were expressed from an MHV backbone lacking the gene for a functional NS2 protein, the endogenous RNase L antagonist. With this system, we found that 2′,5′-PDEs encoded by the human coronavirus HCoV-OC43 (OC43; an agent of the common cold), human enteric coronavirus (HECoV), equine coronavirus (ECoV), and equine torovirus Berne (BEV) are enzymatically active, rescue replication of MHVMut in bone marrow-derived macrophages, and inhibit RNase L-mediated rRNA degradation in these cells. Additionally, PDEs encoded by OC43 and BEV rescue MHVMut replication and restore pathogenesis in wild-type (WT) B6 mice. This finding expands the range of viruses known to encode antagonists of the potent OAS-RNase L antiviral pathway, highlighting its importance in a range of species as well as the selective pressures exerted on viruses to antagonize it. IMPORTANCE Viruses in the family Coronaviridae include important human and animal pathogens, including the recently emerged viruses severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and Middle East respiratory syndrome-associated coronavirus (MERS-CoV). We showed previously that two viruses within the genus Betacoronavirus, mouse hepatitis virus (MHV) and MERS-CoV, encode 2′,5′-phosphodiesterases (2′,5′-PDEs) that antagonize the OAS-RNase L pathway, and we report here that these proteins are furthermore conserved among additional coronavirus superfamily members, including lineage A betacoronaviruses and toroviruses, suggesting that they may play critical roles in pathogenesis. As there are no licensed vaccines or effective antivirals against human coronaviruses and few against those infecting animals, identifying viral proteins contributing to virulence can inform therapeutic development. Thus, this work demonstrates that a potent antagonist of host antiviral defenses is encoded by multiple and diverse viruses within the family Coronaviridae, presenting a possible broad-spectrum therapeutic target.


Author(s):  
V. A. Kotkar, Et. al.

Recently a very strange time to fight with invisible enemy. The Corona virus ailment 2019 also known as COVID-19 outburst, which emerged from Wuhan, the Hubei Province, China, had broaden to all the regions of China and 28 additional countries. Corona viruses are a group of viruses with non segmented, single stranded and positive–sense RNA genomes. Corona viruses is also popular to contaminate human hosts and effect respiratory disease like brutal SARS-CoV (Acute Respiratory Syndrome Corona virus) and MERS-CoV (Middle East Respiratory Syndrome Corona virus). In this paper we discussed on detail analysis of COVID-19 disease.


mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Courtney E. Comar ◽  
Stephen A. Goldstein ◽  
Yize Li ◽  
Boyd Yount ◽  
Ralph S. Baric ◽  
...  

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.


2015 ◽  
Vol 20 (38) ◽  
Author(s):  
Mustafa Kursat Sahin ◽  
Servet Aker ◽  
Ebru Kaynar Tuncel

We performed a questionnaire study to determine knowledge, attitudes and practices concerning Middle East respiratory syndrome (MERS) among people intending to participate in the Hajj or Umrah Muslim pilgrimages. Of the 381 respondents aged between 17 and 85 years, 55% had never heard of MERS, while only one in three knew that it is a respiratory disease. Approximately half were insufficiently informed about protective measures. Prospective pilgrims do not seem prepared to take such precautions.


mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Abeer N. Alshukairi ◽  
Jian Zheng ◽  
Jingxian Zhao ◽  
Atef Nehdi ◽  
Salim A. Baharoon ◽  
...  

ABSTRACT Middle East respiratory syndrome (MERS), a highly lethal respiratory disease caused by a novel coronavirus (MERS-CoV), is an emerging disease with high potential for epidemic spread. It has been listed by the WHO and the Coalition for Epidemic Preparedness Innovations (CEPI) as an important target for vaccine development. While initially the majority of MERS cases were hospital acquired, continued emergence of MERS is attributed to community acquisition, with camels likely being the direct or indirect source. However, the majority of patients do not describe camel exposure, making the route of transmission unclear. Here, using sensitive immunological assays and a cohort of camel workers (CWs) with well-documented camel exposure, we show that approximately 50% of camel workers (CWs) in the Kingdom of Saudi Arabia (KSA) and 0% of controls were previously infected. We obtained blood samples from 30 camel herders, truck drivers, and handlers with well-documented camel exposure and from healthy donors, and measured MERS-CoV-specific enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA), and neutralizing antibody titers, as well as T cell responses. Totals of 16/30 CWs and 0/30 healthy control donors were seropositive by MERS-CoV-specific ELISA and/or neutralizing antibody titer, and an additional four CWs were seronegative but contained virus-specific T cells in their blood. Although virus transmission from CWs has not been formally demonstrated, a possible explanation for repeated MERS outbreaks is that CWs develop mild disease and then transmit the virus to uninfected individuals. Infection of some of these individuals, such as those with comorbidities, results in severe disease and in the episodic appearance of patients with MERS. IMPORTANCE The Middle East respiratory syndrome (MERS) is a coronavirus (CoV)-mediated respiratory disease. Virus transmission occurs within health care settings, but cases also appear sporadically in the community. Camels are believed to be the source for community-acquired cases, but most patients do not have camel exposure. Here, we assessed whether camel workers (CWs) with high rates of exposure to camel nasal and oral secretions had evidence of MERS-CoV infection. The results indicate that a high percentage of CWs were positive for virus-specific immune responses but had no history of significant respiratory disease. Thus, a possible explanation for repeated MERS outbreaks is that CWs develop mild or subclinical disease. These CWs then transmit the virus to uninfected individuals, some of whom are highly susceptible, develop severe disease, and are detected as primary MERS cases in the community.


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