ETIDIOH - NEW

  Abstract The MERS-COV virus is a zoonotic coronavirus that emerged in 2012 in KSA and caused viral illness with a case fatality rate up to 35 %. Over a decade later, the virus is still evolving and circulating . The aim of this review is to discuss the current epidemiology of MERS-COV both in humans and animals, during and post the COVID-19 pandemic. We have found that MERS-COV is still evolving in camels with new lineages being detected in Saudi Arabia . Although the number of human cases has decreased , there is a gradual resurgence in the number of cases. Furthermore, many cases are being reported without exposure to camels and/or raw products, nor contact with known human cases . This necessitates global efforts in the surveillance of asymptomatic carriers in the community, role of unknown animal reservoirs in the virus spread if any, as well as extensive genomic surveillance of the virus. This is in order to unveil and assess the genetic changes that the virus is undergoing ...

  ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal respiratory infection for which no vaccines or antiviral therapeutics are currently available . Understanding the immune response is critical for designing effective therapeutics . Here, we comprehensively characterized the dynamics of B-cell responses in severely infected MERS-CoV patients and survivors with SARS-CoV-2 exposure history . Infected patients developed robust neutralizing antibody responses within 1 month of illness , with moderate-to-high cross-neutralization activity against SARS-CoV-2 . The enhanced neutralization activity coincided with an increased abundance of specific mutated, class-switched IgG clones. Notably, one such clone was detected at moderate prevalence in both patients, and its expansion was accompanied by high neutralization activity against both viruses . Conversely, MERS-CoV survivors demonstrated higher neutralization activity against MERS-CoV after vaccinati...

  ABSTRACT Dromedary camels are the primary reservoir for Middle East respiratory syndrome coronavirus (MERS-CoV), a zoonotic coronavirus responsible for sporadic human infections . While clade B predominates in the Arabian Peninsula and is frequently linked to zoonotic outbreaks and household secondary transmission , clade C circulates primarily in African camels , with limited evidence of human infections . The extent of MERS-CoV transmission, genetic diversity, and cross-species potential in North Africa remains poorly characterized. Here, we investigate MERS-CoV incidence, seroprevalence, and genomic recombination in dromedary camels and sympatric livestock across slaughterhouses and farms in Egypt . MERS-CoV was detected in 12% of camels sampled at slaughterhouses , with no evidence of infection in cattle, buffalo, sheep, or goats . Seroprevalence was higher in slaughtered camels (79%) than camels on farms (12%). Phylogenetic analyses of MERS-CoV genomes obtained from dromedar...

{Automatic translation} The Ministry of Health, Families, Autonomy and Persons with Disabilities and Public Health France have been informed of two cases of MERS-CoV in France .  These two cases were confirmed following suggestive symptoms and a history of shared travel to the Arabian Peninsula .  Management measures have been implemented to limit the risk of virus transmission. Stéphanie Rist, Minister of Health, Families, Autonomy and Persons with Disabilities, confirms: “These patients are being monitored in hospital as a precautionary measure and their condition is stable . All management measures have been put in place to limit the risk of transmission of the virus to the patients' contacts and healthcare staff: contact tracing to offer them follow-up, barrier gestures, testing, isolation and procedures to follow in case of the appearance of symptoms, even mild ones.” These two cases occurred in individuals who had participated in the same trip , but no secondary transmis...

{Summary} Context   Over five years since the detection of the first COVID-19 cases , SARS-CoV-2 continues to circulate globally, causing acute illness, hospitalization, and death , alongside prolonged negative impacts on individuals, health systems , and economies , including post-COVID-19 condition (PCC or Long COVID).  While global population-level immunity has increased significantly through both infection and vaccination, the virus continues to evolve, challenging control efforts and underscoring the need for long-term, sustainable disease management .  Confirming earlier warnings from MERS-CoV and SARS-CoV-1 , SARS-CoV-2 has demonstrated the pandemic potential of coronaviruses , which remain one of the most consequential infectious disease threats of our time .  Purpose of the strategic plan   This plan sets out WHO’s strategic framework to support Member States in the sustained, integrated, evidence-based management of coronavirus disease threats , includ...

  Abstract The membrane (M) protein of coronaviruses is essential for maintaining structural integrity during membrane virion budding and viral pathogenesis . Given its high conservation in lineages within the betacoronavirus genus , such as sarbecoviruses , the M protein presents as an attractive therapeutic target ; however, developing broad-spectrum antivirals targeting coronaviruses such as MERS-CoV is challenging due to lower sequence conservation and limited structural information available beyond that of the SARS-CoV-2 M protein . In this study, we report 3-3.2 Å resolution structures of MERS-CoV M protein, engineered with a SARS-CoV-2-like antibody interface, representing the first human merbecovirus M protein structure , and SARS-CoV M protein structures, with and without a previously identified SARS-CoV-2 M protein inhibitor, JNJ-9676. We highlight the structural differences between the MERS-CoV, SARS-CoV and SARS-CoV-2 M proteins, and present insights into the conservati...

  Abstract The Middle East respiratory syndrome coronavirus (MERS-CoV) remains a highly significant threat to global public health . Dromedary camels are the zoonotic source of human infection. All cases of zoonotic Middle East respiratory syndrome (MERS) have occurred in Middle Eastern countries despite MERS-CoV infection of camels being widespread in Africa . This disparity in the geographic burden of the disease may be due to genomic differences between MERS-CoV circulating in Middle Eastern countries (clades A and B) versus those infecting camels in Africa ( clade C ), although the precise genetic determinants of virulence remain to be elucidated. The objective of the studies reported here was to evaluate differences in the magnitude of virus shedding and in transmissibility of clades A/B and C viruses using alpacas as a surrogate for dromedary camels. We found that two of three African-origin, clade C strains of MERS-CoV induced very reduced levels of virus shedding and were t...

  Abstract Dipeptidyl peptidase-4 (DPP4) is an established receptor for Middle East respiratory syndrome-related coronaviruses (MERSr-CoVs), while recent studies have identified angiotensin-converting enzyme 2 (ACE2) usage in multiple merbecovirus clades . Yet, receptor usage of many genetically diverse bat MERSr-CoVs remains unclear . Here we show that broadly distributed HKU25 clade merbecoviruses use ACE2 , rather than DPP4, as their receptor. Cryo-electron microscopy revealed that HsItaly2011 and VsCoV-a7 strains engage ACE2 similarly to HKU5 but with remodelled interfaces and distinct orthologue selectivity, suggesting a shared evolutionary origin of ACE2 recognition . EjCoV-3, a close relative of the DPP4-using BtCoV422, showed broad multi-species ACE2 tropism and preadaptation to human ACE2 . Several ACE2 glycans and residues within or near the binding interface were identified as determinants of orthologue selectivity. These viruses remain sensitive to several broadly neutr...

  Highlights •  Middle East respiratory syndrome-coronavirus was first detected in 2012 in Saudi Arabia. •  Since 2012, Middle East respiratory syndrome caused 2626 confirmed cases. •  20% of cases involve contact with dromedary camels or their products. •  Human-to-human spread occurs, mainly in healthcare settings. •  A case fatality rate is 36-40%. Source: IJID Regions,  https://www.sciencedirect.com/science/article/pii/S2772707625001663?via%3Dihub ____

  ABSTRACT Cell cultures are widely used to study infectious respiratory diseases and to test therapeutics; however, they do not faithfully recapitulate the architecture and complexity of the human respiratory tract . Lung organoids have emerged as an alternative model that partially overcomes this key disadvantage. Lung organoids can be cultured in various formats that offer potential for studying highly pathogenic viruses . However, the effects of these different formats on virus infection remain unexplored, leaving their relative value unclear. In this study, we generated primary lung organoids from human donor cells and used them to derive monolayers and air-liquid interface (ALI) cultures with the goal of comparing the replication kinetics of two circulating highly pathogenic coronaviruses , severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ) and Middle East respiratory syndrome coronavirus ( MERS-CoV ). Infection studies revealed that organoid-derived monolayers di...

  Abstract Background Bats are recognized as natural reservoir hosts for numerous viruses and are believed to be the evolutionary origin of alpha- and beta-coronaviruses (CoVs), such as SARS-CoV, SARS-CoV-2, and possibly MERS-CoV. MERS-related beta-CoVs have been identified in bat species from Africa, America, Asia, and Europe. In this study, we describe the first detection and characterization of a MERS-related beta-CoV in Danish brown long-eared bats (Plecotus auritus). Methods Fecal samples collected through a national surveillance program were screened using pan-CoV RT-qPCRs. Positive samples underwent ORF1b sequencing, microarray analysis and Illumina MiSeq sequencing, followed by metagenomic assembly of full-length genomes. A global phylogenetic tree was used to determine placement within the Coronaviridae family and local maximum likelihood phylogenetic analysis clarified subgroup placement. The receptor-binding potential of the spike protein to human DPP4, ACE2, and bat ACE...

  Abstract Outbreaks of Middle East respiratory syndrome coronavirus (MERS-CoV) in humans are driven by recurring zoonotic spillover from camels , leading to demand for camel vaccination . With two vaccine candidates shown to reduce infectiousness, there is a need to better understand transmission of MERS-CoV in camels and assess the potential impact of vaccination . To help address this, we used age-stratified seroprevalence data and a combination of modelling methodologies to estimate key epidemiological quantities including MERS-CoV transmissibility in camels and to estimate vaccine impact on infection incidence. Transmissibility was higher in West Asia (R0 interquartile range 7-14) compared to Africa (3-5) and South Asia (2-3), highlighting the need for setting-specific vaccination strategies. Modelling suggested that even if the vaccine only reduced infectiousness rather than susceptibility to infection, vaccinating calves could achieve large reductions in incidence in moderat...

  Abstract SARS-CoV and MERS-CoV are two coronaviruses that have received significant attention due to their high pathogenicity and mortality rates in human populations . In this study, we compared their evolutionary dynamics to provide a One Health perspective on their differences in terms of the results of disease control. The phylogenetic network of SARS-CoVs showed that human isolates gathered into a “super-spreader” cluster and were distinct from civet isolates . In contrast, dromedary camel- and human-isolated MERS-CoVs were clustered together. Thus, most clades of MERS-CoV can infect humans , and MERS-CoVs seem to more easily spill over the animal-to-human interface. Additionally, the civet can be easily controlled , while the intermediate host (dromedary camels) of MERS-CoV is an important livestock species , so it is impossible to eliminate all animals. This further leads to difficulties in disease control in MERS. Although MERS-CoVs are endemic to dromedary camels in both...

Highlights •  MjHKU4r-CoV-1 with high fusogenicity induces inflammatory responses in human cells •  6-HB structure determination unveils MjHKU4r-S-mediated membrane fusion mechanism •  MjHKU4r-CoV-1 HR2 peptides exhibit potent activity by targeting viral HR1 domain •  Stapled peptide MjHKU4r-HR2P10 shows potent and broad-spectrum anti-CoV activity Summary Unlike preceding MERS-related coronaviruses, the recently identified MjHKU4r-CoV-1 strain can directly infect human cells . Nonetheless, its potential pathogenic attributes and underlying molecular mechanisms remain unclear. We find that MjHKU4r-CoV-1 induces significant inflammation , including interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α), and exhibits pronounced fusogenicity mediated by its spike (S) protein, leading to extensive syncytium formation . This suggests the possibility that MjHKU4r-CoV-1 possesses strong pathogenic potential in humans . Further, we successfully reveal the molecular mechan...

Highlights •  Conserved T cell epitope regions elicit strong CD4+ and CD8+ T cell responses in SARS2-exposed •  CTERs enhance cross-reactivity across multiple Betacoronaviruses •  Targeting non-spike proteins expands immune breadth and HLA coverage •  Removing low population coverage regions preserves cross-reactivity Summary The COVID-19 pandemic highlighted the critical need for vaccine strategies capable of addressing emerging viral threats . Betacoronaviruses, including severe acute respiratory syndrome coronavirus ( SARS-CoV ), Middle East respiratory syndrome ( MERS ), and SARS-CoV-2 , present significant pandemic risks due to their zoonotic potential and genetic diversity . T cell-mediated immunity has demonstrated durable responses and strong cross-reactivity, offering a promising avenue for achieving broad immunity within a viral family. In this study, we combined comprehensive epitope mapping with sequence conservation analyses to identify conserved T cell ...

Abstract Background Dromedary camels are known carriers of Middle East respiratory syndrome coronavirus (MERS-CoV). This study aimed to identify respiratory RNA viruses circulating in the nasal cavities of camels that could potentially cause disease in humans. Methods Shotgun metagenomic paired-end sequencing was performed on four pools of nasal swabs collected from 40 camels originating from Sudan and Djibouti, using the MiSeq platform. Results Alphacoronavirus 229E was commonly detected in the camel pools. MERS-CoV was found in both pools from Sudan and one from Djibouti . Camel parainfluenza virus 3 (PIV3) was detected in the male camel pool from Sudan . Furthermore, near-complete (99.9 %) metagenomic assembled genomes (MAGs) of alphacoronavirus 229E (SIAU MAG01) and MERS-CoV (SIAU MAG02) were retrieved from the female camel pool from Sudan . Another MAG of alphacoronavirus 229E (SIAU MAG03) was recovered from a male camel pool imported from Sudan . In the phylogenetic analysis, SIA...

Abstract Identifying receptors for bat coronaviruses is critical for spillover risk assessment, countermeasure development, and pandemic preparedness . While Middle East respiratory syndrome coronavirus ( MERS-CoV ) uses DPP4 for entry , the receptors of many MERS-related betacoronaviruses remain unknown . The bat merbecovirus HKU5 was previously shown to have an entry restriction in human cells . Using both pseudotyped and full-length virus, we show that HKU5 uses Pipistrellus abramus bat ACE2 but not human ACE2 or DPP4 as a receptor. Cryo-electron microscopy analysis of the virus-receptor complex and structure-guided mutagenesis reveal a spike and ACE2 interaction that is distinct from other ACE2-using coronaviruses. MERS-CoV vaccine sera poorly neutralize HKU5 informing pan-merbecovirus vaccine design. Notably, HKU5 can also engage American mink and stoat ACE2 , revealing mustelids as potential intermediate hosts. These findings highlight the versatility of merbecovirus receptor use...

ABSTRACT The threat to global health security posed by Middle East respiratory syndrome coronavirus (MERS-CoV) and emerging MERS-like coronaviruses highlights the need to develop safe and efficient vaccines. Viral vector vaccines have been shown to be effective and are widely used to prevent various viral diseases because they mimic natural infection and induce a more comprehensive immune response. Herein, we developed a novel bat influenza A virus-based vaccine vector by replacing the open reading frame of either bat influenza hemagglutinin or neuraminidase with that of the hemagglutinin-esterase-fusion gene from influenza D virus , which can infect multiple species, including humans and camels . We then generated a temperature-sensitive, cold-adapted, and attenuated MERS vaccine candidate expressing the clade A MERS-CoV spike S1, referred to as Len_S1, using the developed bat influenza vector and demonstrated its safety and immunogenicity. A single-dose intranasal immunization with L...

Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus that causes acute respiratory disease after transmission via close contact with camels . In contrast to the incidence of MERS-CoV human infections in the Middle East , MERS-CoV infections in the Horn of Africa have been rarely reported despite the high number of camels and common camel–human interactions in the area. Whether passive cross-sectional sampling misses active human cases is a significant gap in our understanding of MERS-CoV epidemiology and its impact in the Horn of Africa. To address this gap, we conducted a prospective cross-sectional study at Laisamis Catholic Hospital in northern Kenya’s camel pastoralist community . A total of 942 patients with acute respiratory symptoms were enrolled over 18 months (August 2022–February 2024); 54% of these individuals reported frequent contact with camels and consumption of camel products. Testing via reverse transcriptase – polymerase chain reaction ...

ABSTRACT Betacoronaviruses, which have caused three human outbreaks within the last two decades, are thought to originate from bats , raising the concern that bat coronaviruses could cause a novel human outbreak in the future. To determine whether the bat merbecovirus EjCoV-3 strain , previously detected in Eptesicus japonensis in Japan , has the potential to infect humans, we analyzed its cellular entry mechanism. Cellular entry of EjCoV-3 via the spike protein requires protease treatment and is mediated by an unknown receptor, other than DPP4 or ACE2 . We generated cultivable recombinant EjCoV-3 using bacterial artificial chromosome-based reverse genetics and found that it efficiently replicated in human respiratory and intestinal cell cultures as well as nasal ciliated epithelium in hamsters. These findings suggest that bat merbecovirus with ACE2- and DPP4-independent cell entry has the potential to cause human infections , highlighting the importance of extensive bat surveillance f...