A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques

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

Download Full-text

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Seropositive Camel Handlers in Kenya

Viruses ◽

10.3390/v12040396 ◽

2020 ◽

Vol 12 (4) ◽

pp. 396 ◽

Cited By ~ 1

Author(s):

Alice N. Kiyong’a ◽

Elizabeth A. J. Cook ◽

Nisreen M. A. Okba ◽

Velma Kivali ◽

Chantal Reusken ◽

...

Keyword(s):

Risk Factors ◽

At Risk ◽

High Risk ◽

Middle East ◽

Respiratory Disease ◽

Risk Groups ◽

Middle East Respiratory Syndrome ◽

Limited Evidence ◽

Dromedary Camels ◽

Associated Risk Factors

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.

Download Full-text

Interferon-β and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays

Journal of General Virology ◽

10.1099/vir.0.061911-0 ◽

2014 ◽

Vol 95 (3) ◽

pp. 571-577 ◽

Cited By ~ 114

Author(s):

Brit J. Hart ◽

Julie Dyall ◽

Elena Postnikova ◽

Huanying Zhou ◽

Jason Kindrachuk ◽

...

Keyword(s):

Middle East ◽

Mycophenolic Acid ◽

Rhesus Macaques ◽

Current Treatment ◽

Middle East Respiratory Syndrome ◽

Yield Reduction ◽

Treatment Protocols ◽

Improved Outcomes ◽

Risk Patients

The Middle East respiratory syndrome coronavirus (MERS-CoV) presents a novel emerging threat to public health worldwide. Several treatments for infected individuals have been suggested including IFN, ribavirin and passive immunotherapy with convalescent plasma. Administration of IFN-α2b and ribavirin has improved outcomes of MERS-CoV infection in rhesus macaques when administered within 8 h post-challenge. However, detailed and systematic evidence on the activity of other clinically available drugs is limited. Here we compared the susceptibility of MERS-CoV with different IFN products (IFN-α2b, IFN-γ, IFN-universal, IFN-α2a and IFN-β), as well as with two antivirals, ribavirin and mycophenolic acid (MPA), against MERS-CoV (Hu/Jordan-N3/2012) in vitro. Of all the IFNs tested, IFN-β showed the strongst inhibition of MERS-CoV in vitro, with an IC50 of 1.37 U ml−1, 41 times lower than the previously reported IC50 (56.08 U ml−1) of IFN-α2b. IFN-β inhibition was confirmed in the virus yield reduction assay, with an IC90 of 38.8 U ml−1. Ribavirin did not inhibit viral replication in vitro at a dose that would be applicable to current treatment protocols in humans. In contrast, MPA showed strong inhibition, with an IC50 of 2.87 µM. This drug has not been previously tested against MERS-CoV and may provide an alternative to ribavirin for treatment of MERS-CoV. In conclusion, IFN-β, MPA or a combination of the two may be beneficial in the treatment of MERS-CoV or as a post-exposure intervention in high-risk patients with known exposures to MERS-CoV.

Download Full-text

High Secretion of Interferons by Human Plasmacytoid Dendritic Cells upon Recognition of Middle East Respiratory Syndrome Coronavirus

Journal of Virology ◽

10.1128/jvi.03607-14 ◽

2015 ◽

Vol 89 (7) ◽

pp. 3859-3869 ◽

Cited By ~ 51

Author(s):

Vivian A. Scheuplein ◽

Janna Seifried ◽

Anna H. Malczyk ◽

Lilija Miller ◽

Lena Höcker ◽

...

Keyword(s):

Dendritic Cells ◽

Middle East ◽

Respiratory Disease ◽

Immune Cell ◽

Critical Role ◽

Plasmacytoid Dendritic Cells ◽

Middle East Respiratory Syndrome ◽

Early Gene ◽

Type I ◽

Endosomal Uptake

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.

Download Full-text

Protein Intrinsic Disorder and Evolvability of MERS-CoV

Biomolecules ◽

10.3390/biom11040608 ◽

2021 ◽

Vol 11 (4) ◽

pp. 608

Author(s):

Vladimir N. Uversky ◽

Elrashdy M. Redwan ◽

Abdullah A. Aljadawi

Keyword(s):

Middle East ◽

Respiratory Disease ◽

Intrinsic Disorder ◽

Middle East Respiratory Syndrome ◽

Protein Intrinsic Disorder ◽

Human Coronaviruses ◽

Viral Respiratory

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

Download Full-text

A New-fangled Corona virus coupled with Human Respiratory and AI in COVID-19 Discovery

Turkish Journal of Computer and Mathematics Education (TURCOMAT) ◽

10.17762/turcomat.v12i1s.1545 ◽

2021 ◽

Vol 12 (1S) ◽

pp. 13-22

Author(s):

V. A. Kotkar, Et. al.

Keyword(s):

Middle East ◽

Respiratory Disease ◽

Hubei Province ◽

Middle East Respiratory Syndrome ◽

Corona Virus ◽

Positive Sense ◽

Corona Viruses

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.

Download Full-text

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

mBio ◽

10.1128/mbio.00319-19 ◽

2019 ◽

Vol 10 (2) ◽

Cited By ~ 31

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.

Download Full-text

Knowledge, attitudes and practices concerning Middle East respiratory syndrome among Umrah and Hajj pilgrims in Samsun, Turkey, 2015

Eurosurveillance ◽

10.2807/1560-7917.es.2015.20.38.30023 ◽

2015 ◽

Vol 20 (38) ◽

Cited By ~ 12

Author(s):

Mustafa Kursat Sahin ◽

Servet Aker ◽

Ebru Kaynar Tuncel

Keyword(s):

Middle East ◽

Respiratory Disease ◽

Middle East Respiratory Syndrome ◽

Questionnaire Study ◽

Protective Measures ◽

Attitudes And Practices ◽

Knowledge Attitudes And Practices

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.

Download Full-text