#Human #MERS-CoV #research in the #Gulf Cooperation Council Countries: A mapping scoping review of #epidemiology, #clade, and research priority gaps

 

Abstract

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to pose a substantial public health challenge within Gulf Cooperation Council (GCC) countries. This scoping review systematically examines geographic distribution, methodological characteristics, and thematic priorities of published research, while identifying critical evidence gaps. A total of 171 peer-reviewed studies on human MERS-CoV were included, with a marked predominance from Saudi Arabia (88.3%). Research output peaked in 2016 and 2019, followed by a decline coinciding with the COVID-19 pandemic. Cross-sectional designs were most common (43.3%), with widespread reliance on non-probability sampling (95.3%). Epidemiology and surveillance constituted the primary research focus (∼24%), with case fatality rate being the most frequently reported metric (43.9%). Limited genomic investigations were identified, with Clade B representing 71.4% of characterized strains. Overall, the evidence base reflects geographic concentration, methodological heterogeneity, and thematic limitations, underscoring the need for expanded research scope and enhanced regional collaboration.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S1876034126001449?via%3Dihub

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Loss of nsp14-exonuclease activity impairs the #replication, proofreading, fitness, and #pathogenesis of #SARS-CoV-2

 

ABSTRACT

Coronaviruses (CoVs) replicate their RNA genomes with a higher degree of fidelity than other RNA viruses, a mechanism mediated by the proofreading and recombination activities of the exoribonuclease domain of replicase nonstructural protein 14 (nsp14-ExoN). Both murine hepatitis virus (MHV) and SARS-CoV tolerate nsp14-ExoN loss-of-function mutations (ExoN−) (D90A and E92A), but have impaired replication fidelity and pathogenesis; yet identical substitutions in MERS-CoV and SARS-CoV-2 have been reported to be lethal. Here, we report a saturation mutagenesis approach facilitating the recovery and analysis of several constellations of SARS-CoV-2 nsp14 ExoN-inactivating, loss-of-function substitutions, including the canonical D90A and E92A. Biochemical assays with purified WT or ExoN-nsp10-14 fusion proteins confirmed that active site substitutions abolished ExoN activity (ExoN−). SARS-CoV-2 ExoN− viruses exhibited impaired replication, RNA synthesis, and recombination, as well as decreased replication fidelity and loss of fitness in vitro. ExoN− viruses were significantly attenuated for replication in human primary airway epithelial cells and were attenuated for replication and pathogenesis in WT mice, as well as the highly susceptible K18 transgenic mice. In the absence of interferon signaling in vivo, SARS-CoV and SARS-CoV-2 ExoN− viral replication could be partially restored. These results demonstrate that SARS-CoV-2 ExoN− viruses are viable but highly impaired for replication, fitness, and fidelity in vitro, as well as innate immune antagonism and pathogenesis in vivo. Collectively, our results solidify the multiple critical roles of nsp14-ExoN across CoV genera and establish new approaches for rescuing and analyzing loss-of-function substitutions in studies of CoV replication, pathogenesis, and evolution.

Source: 

Link: https://journals.asm.org/doi/10.1128/mbio.00073-26

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Respiratory #infections due to #human common cold #coronaviruses, #SARS-CoV, #MERS-CoV, and SARS-CoV-2: #epidemiology, #pathogenesis, clinical features, diagnostics, therapeutics, and vaccine landscapes

 

Summary

Over the past half-century, perceptions of human coronaviruses have evolved from their initial characterisation as causes of the common cold to recognition of their capacity to trigger severe disease and global epidemics. The emergence of three zoonotic coronaviruses—severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002, Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, and SARS-CoV-2 in 2019, has had profound health, economic, and societal consequences and continues to influence global epidemic-preparedness strategies. All three viruses remain on the WHO Blueprint of priority pathogens for research and development. This Review summarises current knowledge on human coronaviruses, drawing lessons from the past 25 years of epidemic outbreaks. The shared and divergent features of SARS-CoV, MERS-CoV, and SARS-CoV-2, including their origins, evolution, transmission determinants, zoonotic transmission, viral entry pathways, pathogenesis, spectrum of clinical manifestations, long-term sequelae, and case-fatality profiles are highlighted. The full range of clinical manifestations, from asymptomatic or atypical presentations to severe acute respiratory and multisystem disease, are outlined together with risk factors for progression and populations with the greatest susceptibility. Diagnostic approaches, including molecular assays, antigen-based tests, and imaging modalities are described alongside current therapeutics, antiviral strategies, immunomodulators, supportive care principles, and evidence from clinical trials. Advances in diagnostics, vaccines, therapeutics, and infection-control practices are examined together with persistent challenges in early recognition, particularly in resource-limited settings. Strengthening multinational clinical trial capacity, leveraging digital innovations, and embedding One Health approaches are essential to mitigating spillover risks and improving global readiness. We review the latest data, identify gaps and opportunities, and outline forward-looking strategies to anticipate and prepare for the threat of future coronaviruses, and other existing or new respiratory pathogens with epidemic potential. Clinicians and other health-care workers play a central role in detecting and reporting possible lethal coronavirus infection including atypical presentations, enabling rapid, coordinated infection control and management responses.

Source: 

Link: https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(26)00049-4/abstract?rss=yes

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Operational #zoonotic #containment of #MERS #coronavirus in #Saudi Arabia: An implementation-oriented #OneHealth genomic #framework

 

Abstract

Background and Aim: 

Middle East respiratory syndrome coronavirus (MERS-CoV) remains a persistent zoonotic threat more than a decade after its first detection, with Saudi Arabia continuing to be the global epicenter of human infections and the main reservoir interface through dromedary camels. Despite ongoing surveillance, advances in molecular diagnostics, and research on vaccines and therapeutics, sporadic zoonotic spillovers and healthcare-associated outbreaks still occur, showing that current prevention strategies are still not enough. This review compiles current evidence from epidemiological studies, camel reservoir research, genomic monitoring, and public health reports published between 2012 and April 2025 to identify the key gaps preventing effective containment. Special focus is given to recent genomic discoveries, including post-2022 clade B sublineages, recombination events, and spike protein changes that might affect transmission and the effectiveness of countermeasures. Available data suggest that MERS-CoV epidemiology is driven by repeated camel-to-human transmission, followed by occasional amplification in healthcare settings rather than sustained community spread. High seroprevalence and frequent detection of viral RNA in juvenile camels, seasonal gathering in markets, and extensive animal movement networks contribute to ongoing viral circulation at the animal–human interface. Genomic studies consistently show close phylogenetic relationships between camel and human isolates, confirming recurrent zoonotic transmissions. However, fragmented surveillance systems, delayed genomic data integration, inconsistent biosecurity practices, and limited field evidence for camel vaccination pose major barriers to control. Additionally, hospital outbreaks continue to occur due to delayed diagnosis, overcrowding, and incomplete adherence to infection-prevention protocols, underscoring the need for improved clinical preparedness. Based on the integrated synthesis of epidemiological, veterinary, and genomic evidence, this review proposes an implementation-focused One Health genomic framework tailored to the Saudi context. The proposed roadmap highlights real-time connection of human and camel surveillance, expands genomic sequencing capacity, targets vaccination strategies in camels and high-risk human populations, standardizes biosecurity measures in markets and abattoirs, and strengthens infection control systems in healthcare facilities. Alignment with national governance structures and Saudi Vision 2030 offers a practical pathway for coordinated multi-sectoral action. This review concludes that MERS-CoV is unlikely to be eradicated soon, but it can be effectively managed through a genomics-enabled, operational One Health approach that combines surveillance, vaccination, clinical preparedness, and policy coordination. The model outlined here provides a scalable way to reduce zoonotic spillover risk and strengthen readiness against future coronavirus and emerging zoonotic threats. 

Source: 

Link: https://veterinaryworld.org/Vol.19/March-2026/29.php

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A natural five-amino-acid insert at the S2’ #cleavage site of #MERS-CoV #spike enhances viral membrane fusion

 

Highlights

• A novel 5-aa insert, TSGVF, is present at the S2’ cleavage site of the spike protein of MERS-CoV from dromedary camels.

• Pseudovirus-based entry assays showed that the TSGVF insert increases viral entry efficiency in different human cells.

• Pseudovirus with TSGVF insert at the S2’ cleavage site showed strong resistance to TMPRSS2 inhibitor.

• The natural occurrence of TSGVF insert at the spike S2’ cleavage site enhances viral membrane fusion and syncytia formation.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S1995820X26000611?via%3Dihub

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#SARS-CoV-2 and #MERS-CoV disrupt #host #protein synthesis via nsp1 with differential effects on the integrated stress response

 

Significance

Coronaviruses cause disease across a wide range of animal species and the human coronaviruses SARS-CoV-2 and MERS-CoV have caused epidemics of severe respiratory illness. Thus, it is imperative to understand how these viruses antagonize host responses and cause lethal disease. We show here that the betacoronavirus nonstructural protein 1 (nsp1) promotes shutdown of host protein synthesis while preserving viral protein synthesis and, in addition, promotes degradation of host mRNAs. However, SARS-CoV-2 and MERS-CoV differ in their ability to manipulate the host integrated stress response, indicating that it is important to understand detailed coronavirus–host interactions and how they differ even between lethal coronaviruses. Such insights will inform the development of antiviral therapeutics to treat and prevent current and future coronavirus outbreaks.

Abstract

Coronaviruses pose a serious threat to public health, driving the need for antiviral therapeutics and vaccines. Therefore, it is paramount to understand how this family of viruses evades cellular antiviral responses and establishes productive infection. The conserved coronavirus nonstructural protein 1 (nsp1) has been shown to inhibit host protein synthesis and, in some coronaviruses, promote host messenger RNA (mRNA) degradation while viral mRNAs are protected. We showed previously that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induces activation of host integrated stress response (ISR) kinases protein kinase R (PKR) and PKR-like endoplasmic reticulum kinase (PERK), which promote phosphorylation of eukaryotic initiation factor 2 (eIF2α) and consequent inhibition of host protein synthesis. In contrast, eIF2α remains unphosphorylated during Middle East respiratory syndrome coronavirus (MERS-CoV) infection. To investigate the interactions of nsp1 and the ISR kinases, we utilized recombinant SARS-CoV-2 and MERS-CoV expressing nsp1 with mutations in each of two conserved domains. Upon infection with SARS-CoV-2 nsp1 mutants, translation was shut down in wildtype (WT) and PKR knockout (KO) cells but rescued in PERK KO cells, likely due to reduced p-eIF2α. In contrast, translation was rescued during infection with the analogous MERS-CoV nsp1 mutants even in WT cells. Moreover, SARS-CoV-2 WT suppressed expression of GADD34, a negative regulator of eIF2α phosphorylation, while SARS-CoV-2 nsp1 mutants induced GADD34. In contrast, MERS-CoV WT induced GADD34. Utilizing single-molecule fluorescence in situ hybridization, we found that SARS-CoV-2 and MERS-CoV nsp1 promote host mRNA degradation during WT, but not nsp1 mutant, infection. Thus, SARS-CoV-2 and MERS-CoV differ in interactions with the ISR and nsp1 control of host protein synthesis.

Source: 

Link: https://www.pnas.org/doi/abs/10.1073/pnas.2536296123?af=R

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Q1020R in the #spike proteins of #MERS-CoV from Arabian #camels confers resistance against soluble #human #DPP4

 

ABSTRACT

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a pre-pandemic coronavirus that is transmitted from camels, the natural reservoir, to humans and can cause severe disease. MERS cases have been documented in Arabia but not Africa, although the virus is circulating in both Arabian and African camels. Further, evidence has been provided that viruses in African camels might have a reduced capacity to cause disease. However, the underlying determinants are incompletely understood. Here, employing pseudotyped particles as model systems for MERS-CoV entry into cells, we compared cell entry of viruses from African and Arabian camels and its inhibition. We show that viruses found in Arabian camels and recent human cases are less susceptible to inhibition by human soluble DPP4 (sDPP4) than viruses from African camels, although both enter human cells efficiently and are comparably sensitive to inhibition by interferon-induced transmembrane (IFITM) proteins and neutralizing antibodies. Furthermore, relative resistance to sDPP4 was linked to mutation Q1020R, present in the spike proteins of recent Arabian but not African viruses. Finally, indirect evidence was obtained that sDPP4 in human plasma can inhibit MERS-CoV cell entry. These results support the concept that soluble DPP4 might constitute a natural barrier against human infection that is more efficiently overcome by viruses currently circulating in Arabian camels than those in African camels.

Source: 

Link: https://journals.asm.org/doi/10.1128/jvi.00282-26

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Next-generation #inhibitors of #SARS-CoV-2 #Mpro overcome the deficiencies of #Paxlovid

 

Abstract

It remains elusive to design peptidomimetic inhibitors of SARS-CoV-2 main protease (Mpro) refractory to multiple deficiencies of Paxlovid (ritonavir-boosted nirmatrelvir), pertaining mainly to E166X mutations-conferred drug resistance and inherent pharmacokinetic limitations to nirmatrelvir. We identify via virtual screening an iso-quinoline P1 moiety in place of the traditional γ-lactam and design iso-quinoline-containing inhibitors with high affinity for Mpro and its nirmatrelvir-resistant E166X mutants. Further optimization at P4 cultivates distinctive peptidomimetic inhibitors with drastically improved pharmacokinetic properties and significantly enhanced antiviral efficacy independent of ritonavir. Two such inhibitors, FD3-32 and FD3-36, also potent against SARS-CoV-1 and MERS-CoV Mpro, are more effective as a monotherapy regimen than Paxlovid in reducing viral loads in vivo and protecting infected male mice from acute lung injury. Here, we report the discovery of next-generation SARS-CoV-2 Mpro inhibitors that overcome the deficiencies of Paxlovid, promising efficacious antivirals critical for mitigating the current and future pandemics of coronaviruses.

Source: 

Link: https://www.nature.com/articles/s41467-026-71436-6

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Clade C #MERS-CoV #camel #strains vary in #protease utilization during viral entry

 

Significance

Clade A/B Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreaks have caused over 957 deaths since the first spillover in 2012; meanwhile, Clade C strains have been found in camels across Africa but have not yet been reported to cause outbreaks. Investigating why these viruses do not successfully transmit to humans will be key to understanding the pandemic potential of the African MERS-CoV camel reservoir. Our study indicates that clade C viruses exhibit less spike cleavage and that East African clade C isolates are less able to utilize the TMPRSS2 for viral entry of both human cell lines and primary nasal cells. Differences in viral entry pathways could alter cellular and organ tropism and contribute to differential pandemic potential.

Abstract

Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a lethal pathogen with pandemic potential. Clade A and B MERS-CoV viruses have caused outbreaks in the Middle East since 2012 when they initially spilled over from camels to humans. Clade C viruses, however, are only found in camels across Africa and the spillover potential of these viruses seems to be lower than for clade A/B strains but remains to be fully understood. Here, we report that clade C spikes are less well-cleaved at the S1/S2 boundary than clade A or B viral spikes and that most clade C spikes induce reduced syncytium formation. Additionally, we demonstrate that several East African clade C strains are less able to utilize the TMPRSS2-mediated pathway for viral entry in both cell lines and primary nasal epithelial cultures. We map the molecular basis of this reduced TMPRSS2 usage to the N-terminal domain and subdomain 2 of East African clade C MERS-CoV. We suggest that reduced usage of the TMPRSS2-mediated entry pathway may underlie the reduced replication of East African clade C strains in humans, while the reduced replication of West African strains remains to be further investigated. Altered protease usage may contribute to differential tropism of East African clade C strains and indicate geographically distinct selection pressures on spike between MERS-CoV strains circulating in camels.

Source: 

Link: https://www.pnas.org/doi/10.1073/pnas.2525313123

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Characterisation of Naturally Occurring #MERS-CoV #Spike #Mutations and Their Impact on #Fusion and Neutralisation

 

Abstract

In this study, the phenotypic consequences of naturally occurring single nucleotide polymorphisms (SNPs) in the Middle East respiratory syndrome coronavirus (MERS-CoV) Spike protein were investigated. The impact of Spike mutations on the syncytia formation and neutralisation of contemporary MERS-CoV strains is not currently well understood. Mutations were identified by aligning 584 MERS-CoV Spike sequences from either human clinical isolates collected between 2012 and 2024 or from a clinical isolate that had been passaged in human cells. Fifteen SNPs of interest occurring in the N-terminal domain (NTD), receptor binding domain (RBD) and adjacent to the S1/S2 cleavage site were selected for further characterisation based on their location in the Spike protein, frequency and identification in previous studies. A contemporary clade B, lineage 5 wildtype Spike sequence, obtained from a human MERS-CoV clinical isolate, was used as the backbone in this study. The mutations of interest were introduced to the wildtype backbone to generate Spike variants. Spike variants were characterised via cell–cell fusion assays, and a lentiviral pseudotyping system was used to investigate the impact of these Spike mutations on neutralisation. The I529T, E536K and L745F mutations were shown to increase fusion and syncytia formation. The L411F, T424I, L506F, L745F and T746K mutations were found to increase resistance to neutralisation by pooled patient sera. This study has identified novel naturally occurring Spike mutations that resulted in phenotypic differences in the syncytia formation and neutralisation of contemporary MERS-CoV strains. Continued investigation of the phenotypic consequences of MERS-CoV Spike mutations is essential for assessing the risk to public health, especially given the pandemic potential of this virus.

Source: 

Link: https://www.mdpi.com/1999-4915/18/3/377

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Middle east respiratory syndrome coronavirus (#MERS-CoV): An underestimated #betacoronavirus with #pandemic potential

 

Highlights

• MERS-CoV remains an endemic camel-associated betacoronavirus with ongoing zoonotic spillover.

• Viral evolution shows three major clades with lineage B predominance and documented recombination.

• DPP4-mediated entry, immune suppression, and T-cell apoptosis drive severe disease and high fatality.

• Diagnosis relies primarily on rRT-PCR, while treatments and vaccines remain experimental.

• Strengthened One-Health surveillance, IPC, and genomic monitoring are essential for pandemic preparedness.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic beta coronavirus identified in 2012 that circulates in dromedary camels and occasionally infects humans. Although community spread is limited, the disease shows a high case fatality rate near 36 percent and has caused hospital outbreaks such as the 2015 South Korea event. The viral spike binds the DPP4 (CD26) receptor, enabling entry into airway epithelial and selected immune cells, while accessory proteins suppress early innate immunity. Genetic studies indicate continuing evolution with clades A, B, and C across the Arabian Peninsula and Africa. Human infection is linked to camel contact, farm exposure, or raw camel products, with secondary spread mainly in healthcare settings. Diagnosis uses rRT-PCR and serology; treatment is supportive, and vaccines and antivirals are under study. A One Health approach is vital for surveillance, early detection, and control.

Source: Diagnostic Microbiology and Infectious Disease, https://www.sciencedirect.com/journal/diagnostic-microbiology-and-infectious-disease

Link: https://doi.org/10.1016/j.diagmicrobio.2026.117367

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#MERS #Coronavirus–Specific T-Cell Responses in Dromedary #Camel #Abattoir #Workers in #Nigeria Suggests Frequent Zoonotic #Spillover

 

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is assessed to have high pandemic risk, and dromedary camels are the source of zoonotic spillover. More than 75% of MERS-CoV–infected dromedary camels are found in Africa, but no zoonotic disease has been reported from Africa where there is little awareness of MERS-CoV as a potential cause of respiratory disease. Antibody responses are a poor indicator of mild infection. We found that 47 of 60 (78%) dromedary camel abattoir workers in Kano, Nigeria, had MERS-CoV–specific T-cell responses while none of 18 controls did, suggesting that zoonotic infection is common in camel-exposed individuals in Africa.

Source: 

Link: https://academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiag095/8504072?redirectedFrom=fulltext

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Unveiling the #epitope #repertoires and protective roles of #MERS-CoV-specific T cells in mice

 

Highlights

• MERS-CoV structural proteins and ORFs potently induce T cell responses in mice

• MERS-CoV-specific T cell epitope repertoires are identified in C57BL/6 and BALB/c mice

• Airway ORF4b208-CD4+ and ORF5167-CD8+ T cells are optimal effector T cells

• ORF4b208 and ORF5167-specific T cells protect mice against MERS-CoV infection

Summary

Since its initial emergence in 2012, MERS-CoV has remained endemic and a global health threat. While accessory proteins (ORFs) are known for immune evasion, their role in adaptive immunity is unexplored. This study systematically investigated T cell responses against MERS-CoV ORFs. We mapped epitope repertoires targeting structural proteins and ORFs in C57BL/6 and BALB/c mice, revealing that ORFs potently induced virus-specific T cells. Notably, ORF5 induced the dominant CD8+ T cell responses in BALB/c mice. Further analysis revealed that ORF4b208-specific CD4+ and ORF5167-specific CD8+ T cells in the respiratory tract exhibited polyfunctional cytokine profiles, high antigen sensitivity, and potent in vivo cytotoxicity. These specific T cells played protective roles during MERS-CoV infection by promoting viral clearance. Collectively, this study identified MERS-CoV-specific T cell epitopes and elucidated the roles of ORF4b- and ORF5-specific T cells, enhancing our understanding of anti-MERS-CoV T cell responses and advancing vaccine design strategies against MERS-CoV.

Source: 

Link: https://www.cell.com/cell-reports/fulltext/S2211-1247(26)00121-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS221112472600121X%3Fshowall%3Dtrue

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Decoding #antibody response to #MERS-CoV in wild dromedary #camels

 

Significance

Middle East respiratory syndrome coronavirus (MERS-CoV) remains the most lethal human coronavirus, with continued zoonotic transmission from wild naturally infected dromedary camels, posing a persistent risk of spillover to humans. Despite this ongoing threat, no specific antiviral treatment has been approved. In this study, we characterize the antibody response to MERS-CoV in naturally infected dromedaries, the primary animal reservoir, and identify a panel of nanobodies (Nbs) exhibiting potent neutralizing activity. These Nbs recognize a previously unreported binding and neutralizing site on the virus spike receptor-binding domain (RBD). Their distinctive genetic, structural, and functional properties make them promising candidates for the development of effective and therapeutic interventions against MERS-CoV, as strongly advocated by global health authorities.

Abstract

Wild dromedary camels in the Arabian Peninsula and Africa have harbored antibodies against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) for decades, predating zoonotic spillover to humans. However, the potency, specificity, and structural characteristics of these antibodies remain poorly understood. Here, we characterize the antibody responses of naturally infected wild dromedary camels in Tunisia, a MERS-CoV-endemic region. Plasma antibodies from nine camels exhibited variable neutralizing activity, generally increasing with age, and were largely autologous, with minimal cross-reactivity to SARS-CoV-1 or SARS-CoV-2. From a VHH antibody library derived from the peripheral blood mononuclear cells (PBMCs) of a single camel (D17), we identified 34 unique sequences with previously unreported germline origins and unusually long complementarity-determining region 3 (CDR3) sequences. Eight representative VHHs, expressed as human Fc fusions, displayed high-affinity binding to the MERS-CoV receptor-binding domain (RBD) and broad neutralization to RBD mutants (IC50: 1.05 to 9.55 ng/mL). Crystal structural analysis revealed distinct neutralization mechanisms: VHH-227 fully blocked DPP4 binding, achieving complete neutralization, while VHH-T71, with partial neutralization (~80%), targeted the RBD core subdomain. This study provides comprehensive characterization of wild dromedary antibody responses, identifying novel nanobodies (Nbs) with broad and potent neutralization to naturally occurring RBD mutants. These findings offer insights into camel immunity and highlight promising candidates for MERS-CoV prophylactic and therapeutic development.

Source: 

Link: https://www.pnas.org/doi/10.1073/pnas.2513716123

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#Epidemiology and #genomic features of #MERS #coronavirus in #Africa: a systematic and meta-analysis review

 

Highlights

• 74% pooled MERS-CoV seroprevalence in African dromedaries

• Highest MERS-CoV RNA incidence (15.3%) observed in juvenile dromedaries

• 2.4% pooled MERS-CoV seroprevalence in camel-exposed humans

• African MERS-CoV clade C exhibits unique polymorphisms

• Clade-specific features might explain low MERS-CoV infection rates in Africa

Abstract

Objective

We explored factors contributing to the low human MERS-CoV prevalence in Africa by assessing MERS-CoV epidemiological and genomic features.

Methods

We followed the PRISMA guidelines. We searched for articles on epidemiological and virological MERS-CoV characteristics in humans and camels in Africa until August 2025. We used a generalised linear mixed-effects model to calculate pooled proportions. We identified relevant polymorphisms in African MERS-CoV lineages compared with the prototypic EMC/2012 and contemporary Arabian MERS-CoV (clade B5).

Results

We included 53 articles, with 31 used in the meta-analysis. Kenya, Egypt, and Ethiopia contributed to 66.03% of all included studies. Pooled MERS-CoV RNA positivity in African dromedaries was 6.09%, with juveniles (15.29%) having a higher incidence than adults (4.51%). The pooled MERS-CoV seroprevalence was 73.67%, with adults (80.96%) higher than juveniles (36.02%). In human-focused studies, only nine PCR-confirmed MERS cases were reported, six travel-associated and three autochthonous cases, despite a pooled seroprevalence of 2.4%. Genomic analyses identified MERS-CoV clade C-specific polymorphisms in the Spike and accessory genes with putative phenotypic impact.

Conclusion

We found the highest MERS-CoV RNA positivity in young dromedaries. Elevated MERS-CoV seroprevalence in mainly asymptomatic camel-exposed humans suggests an underestimation of MERS-CoV infections in Africa. The ongoing MERS-CoV evolution emphasises the need for active genomic surveillance to monitor signatures of human adaptation.

Source: 

Link: https://www.ijidonline.com/article/S1201-9712(26)00091-3/fulltext

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A stabilized #MERS-CoV #spike ferritin #nanoparticle #vaccine elicits robust and protective neutralizing #antibody responses

 

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as a human pathogen in 2012 and causes ongoing sporadic infections and outbreak clusters. Despite case fatality rates (CFRs) of over 30% and considerable pandemic potential, a safe and efficacious vaccine has not been developed. Here we report the design, characterization, and preclinical evaluation of MERS-CoV antigens. Our lead candidate comprises a stabilized spike displayed on a self-assembling ferritin nanoparticle that can be produced from a high-expressing, stable cell pool. This vaccine elicits robust MERS-CoV pseudovirus and authentic virus neutralizing antibody titers in BALB/c mice. Immunization of male non-human primates (NHPs) with one dose of Alhydrogel-adjuvanted vaccine elicited a > 103 geometric mean titer of pseudovirus neutralizing antibodies that was boosted with a second dose. Sera from these NHPs exhibited cross-reactivity against spike-pseudotyped lentiviruses from MERS-CoV clades A, B, and C as well as a distant pangolin merbecovirus. In human DPP4 transgenic mice, immunization provided dose-dependent protection against MERS-CoV lethal challenge, and in an established alpaca challenge model using female alpacas, immunization fully protected against MERS-CoV infection. This MERS-CoV nanoparticle vaccine is a promising candidate for clinical advancement to protect at-risk individuals and for future use in a potential outbreak setting.

Source: 

Link: https://www.nature.com/articles/s41467-026-68458-5

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The #impact of clade B #lineage 5 #MERS #coronaviruses #spike #mutations from 2015 to 2023 on virus entry and replication competence

 

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging coronavirus that can cause zoonotic disease in humans with lethal severe viral pneumonia. Dromedary camels are the source of zoonotic infection. As of November 2025, MERS-CoV has resulted in a total of 2630 reported cases, 37% of these being fatal. The number of reported human cases has been on a decreasing trend since 2016 and reached a nadir during the COVID-19 pandemic. The reason for the reduction of cases is unclear and may be multifactorial. We hypothesized that mutations accumulating in the virus spike protein may have reduced zoonotic potential. Here, we investigate the impact of recently emerged virus spike-protein mutations on virus replication competence using pseudoviruses and replication-competent recombinant viruses. We found that virus spike variants detected in 2019 and some from 2023 show a reduced cell entry, lower viral replication and reduced fitness in human primary alveolar epithelial cells and multiple cell lines. All the MERS-CoV spikes tested showed a cell-entry pathway preference via the cell-surface TMPRSS2 route. Mechanistically, we showed the V530A mutation in the 2019 spike sequence had a reduced human DPP4 binding phenotype. Our data highlighted MERS-CoV spike mutations can modulate viral fitness in human cells and provide new insights to understand recent MERS epidemiology.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013336

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Rapid #Risk #Assessment - #MERS-CoV, Eastern Mediterranean Region (#WHO, Feb. 3 '26, summary)

 

Risk statement  

-- The scope of this Rapid Risk Assessment is to reassess the epidemiological situation of Middle East respiratory syndrome coronavirus (MERS-CoV) following the recent exportation (in December 2025) of cases from the Arabian Peninsula to France and three healthcare-associated clusters reported by the Kingdom of Saudi Arabia (KSA) in 2024–2025. 

-- These events, together with the continued occurrence of sporadic cases in Arabian Peninsula countries, highlight the ongoing risk of international spread to non-endemic countries and reflect the persistent circulation of MERS-CoV in the Middle East.  

-- Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus transmitted to humans through direct or indirect contact with infected dromedary camels, which are the natural host of the virus. 

-- First identified in humans in 2012 in the Kingdom of Saudi Arabia (KSA) and Jordan, MERS-CoV causes a viral respiratory infection that occurs throughout the year, with cases reported sporadically and in clusters. 

-- Clinical presentation ranges from asymptomatic or mild respiratory illness to severe acute respiratory disease, pneumonia, and death. 

-- The case fatality rate among cases reported to WHO is 37%.    

-- Since MERS-CoV emergence in 2012, until 23 January 2026, under the International Health Regulations (IHR, 2005), 27 countries have reported human cases of MERS-CoV to the WHO: 

- Algeria, 

- Austria, 

- Bahrain, 

- China, 

- Egypt, 

- France, 

- Germany, 

- Greece, 

- the Islamic Republic of Iran, 

- Italy, 

- Jordan, 

- Kuwait, 

- Lebanon, 

- Malaysia, 

- the Netherlands, 

- Oman, 

- the Philippines, 

- Qatar, 

- the Republic of Korea, 

- the Kingdom of Saudi Arabia (KSA), 

- Thailand, 

- Tunisia, 

- Türkiye, 

- the United Arab Emirates (UAE), 

- the United Kingdom, 

- the United States of America, and 

- Yemen.    

-- However, of the 2635 MERS cases documented globally since 2012, 2418 (92%) were reported from the WHO Eastern Mediterranean Region (EMR). 

-- The majority (84%) of reported cases were notified by KSA (2224/2635) followed by other Arabian Peninsula countries: the UAE (94), Jordan (28), Qatar (28), Oman (26), Iran (6), Kuwait (4), Tunisia (3), Lebanon (2), Bahrain (1), Egypt (1) and Yemen (1).  

-- Exposure was commonly linked to direct or indirect contact with infected dromedary camels or transmission from infected individuals in healthcare settings or households. 

-- Most cases reported outside the Arabian Peninsula countries involved people likely infected there prior to travelling elsewhere.    

-- Following the first human infection with MERS-CoV in 2012, the Director‐General convened an Emergency Committee under the International Health Regulations (IHR 2005) in 2013 to assess whether the outbreaks of MERS constituted a Public Health Emergency of International Concern (PHEIC) and to provide guidance on the public health measures that should be taken.{i}  

-- The Committee has met on 10 occasions and, on each occasion, concluded that the outbreaks do not meet the criteria of a PHEIC.    

-- The overall risk of MERS-CoV in 2023 was assessed as moderate both at the regional and global levels.  

-- A new assessment currently confirms that this risk level remains unchanged, moderate both at the regional and global levels, taking into account the following considerations:  

- 1. Continued reports of sporadic cases in endemic countries in the Arabian Peninsula and the occasional occurrence of traveller cases and healthcare-associated transmission, including two cases reported from France in December 2025 and three clusters reported in the Kingdom of Saudi Arabia during 2024–2025. 

- 2. Since the last RRA in 2023, cases reported to WHO have not resulted in sustained onward human-tohuman transmission, as most identified close contacts tested negative and no additional household clusters have been identified. The three healthcare-related clusters remained limited, with infection only confirmed in direct contacts with the index case. 

- 3. The observed decline in reported MERS cases since 2020, in particular during the COVID-19 pandemic emergency phase, is thought to be a result of pandemic-related Infection Prevention & Control measures that also limited human-to-human transmission of MERS-CoV, as well as behavioural changes during the pandemic. Any role of potential cross-reactive immunity from SARS-CoV-2 infection and/ or vaccination remains in need of further investigation. Other hypotheses—such as reduced surveillance, viral attenuation, or decreased circulation in camel populations—are not supported by current evidence. 

- 4. Significant disparities persist globally in countries' capacities to detect and respond effectively to the disease, particularly in regions where the virus has not been previously documented. Within the EMR, six fragile, conflict-affected, and vulnerable countries are considered at greater risk.  

- 5. Global inequalities remain in the adequacy of preparedness, infection prevention and control capacities, and response measures, particularly in the context of a cross-border outbreak or a traveller case.  

- 6. MERS-CoV continues to circulate in dromedary camel populations without causing overt clinical signs, constituting a constant source of human exposure and a risk of zoonotic spillover, which may result in occasional onward human-to-human transmission. The recent detection of Clade B viruses in camels of African origin further highlights the risk of MERS-CoV spread from the Arabian Peninsula via camel movements and poses an additional risk to other regions, particularly given the documented increased replication competence and more efficient viral entry of Clade B compared with Clade C. 

- 7. Preliminary data from in vitro growth kinetics and partial sequencing indicate no major attenuation in circulating Clade B strains. 

- 8. The potential public health impact of MERS-CoV should not be underestimated given the severity of disease and its high reported case fatality rate (CFR), even though sustained global spread is currently considered unlikely.  

- 9. MERS-CoV can cause severe disease resulting in high mortality. The current CFR of 37% is based on laboratory-confirmed cases only and may therefore overestimate of the true mortality rate.  

- 10. Existing regional and global surveillance systems may fail to detect asymptomatic and mild cases of MERS, leading to underreporting.  

- 11. Limited and non-sustained human-to-human transmission has been documented, mainly in healthcare and household settings. However, due to limited research, data gaps remain in understanding transmission dynamics, including the role of environmental contaminations, asymptomatic cases and specific exposure risk in healthcare settings. Further research is needed to better understand zoonotic transmission associated with dromedary camel products and excreta.  

- 12. Due to the similarity of symptoms with other respiratory diseases that are widely circulating, like influenza or COVID-19, detection and diagnosis of MERS cases may be delayed, especially in unaffected countries, creating opportunity for local onward transmission.  

- 13. Should MERS-CoV result in a healthcare-associated outbreak in a previously unaffected country, as occurred in the Republic of Korea in May 2015, during which 186 laboratory-confirmed cases (185 in the Republic of Korea and 1 in China) and 38 deaths were reported, the public health consequences for that country could be substantial.  

- 14. The recent exportation of cases from the Arabian Peninsula to France demonstrates the ongoing risk of international spread. 

(...)

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{1} Confidence refers to the level of confidence in the data/information or the quality of the evidence available at the time the RRA is conducted. Poor quality information may increase the overall perceived risk due to the incertitude in the assessment 

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Source: 

Link: https://www.who.int/publications/m/item/who-rapid-risk-assessment-mers-cov--eastern-mediterranean-region-v.2

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Structural basis for #human #DPP4 #receptor recognition by #MERS-like #coronaviruses 2014-422 and GX2012

 

Abstract

Since its emergence in 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has posed a significant threat to human health. Recently, novel MERS-like coronaviruses with the potential for cross-species transmission have been identified. In this study, we focused on two newly isolated bat strains with putative health concern: BatCoV/Ii/GD/2014-422 (2014-422) and BtTp-BetaCoV/GX2012 (GX2012). We determined the cryo-EM structures of the spike glycoprotein trimer in the closed state for these two viruses. These structures display a more compact conformation compared to MERS-CoV spike. Biochemical characterization demonstrates that the spike receptor-binding domains (RBDs) of 2014-422 and GX2012 can bind to human dipeptidyl peptidase 4 (hDPP4). To investigate the structural determinants of pseudovirus infection, we solved the cryo-EM structures of 2014-422 RBD-hDPP4 and GX2012 RBD-hDPP4 complexes. The binding mode of the complex is conserved, but the angle of the RBD binding undergoes significant tilting. Detailed structural analysis reveals that an additional residue at position 514 interacts with the N321 glycan in hDPP4, altering the binding angle and thus influencing receptor recognition. These findings offer valuable insights into the receptor utilization of Merbecovirus and provide a structural basis for future surveillance efforts.

Author summary

Two MERS-like coronaviruses, BatCoV/Ii/GD/2014-422 (2014-422) and BtTp-BetaCoV/GX2012 (GX2012), have recently emerged as potential zoonotic threats. In this study, we provide a detailed structural analysis of these two viruses, focusing on their spike proteins and interactions with human Dipeptidyl Peptidase 4 (hDPP4), the receptor used by MERS-CoV. Using cryo-electron microscopy (cryo-EM), we determined high-resolution structures of 2014-422 and GX2012 spike glycoproteins in their closed conformations. Our results show that GX2012 mediates efficient pseudovirus entry into human cells, whereas 2014-422 shows markedly reduced entry efficiency. This difference is linked to structural variations, including a unique residue at position 514 in both viruses that affects the RBD binding angle and receptor recognition. Together, these findings provide key insights into the structural basis of receptor usage by MERS-like coronaviruses and suggest that HKU4r-CoVs may acquire the ability to infect human cells through two evolutionary routes: within bats and through pangolins as intermediate hosts.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013792

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Phylogenetic Characteristics and High Prevalence of a #Merbecovirus in #Hedgehogs from Greenspace of a Metropolis, #China

 

Abstract

SARS-CoV, MERS-CoV, and SARS-CoV-2 have posed tremendous threats to human health, highlighting the necessity of monitoring cross-species transmission of animal coronaviruses to humans. Hedgehogs infected with coronaviruses have been reported in several countries across Europe and Asia, raising concerns about the potential transmission of coronaviruses from hedgehogs to humans. In this study, we investigated coronavirus infections in hedgehogs inhabiting greenspaces in metropolitan Beijing and identified a Merbecovirus subgenus coronavirus with a prevalence rate of 30% (95% CI: 25–35%) among 317 hedgehogs. Phylogenetic analysis of 23 complete viral genome sequences revealed a monophyletic origin, showing close relatedness to Erinaceus hedgehog coronavirus HKU31 (Ea-HedCoV HKU31) with genome-wide nucleotide identities of 93.24–96.42%, and evidence of recombination with Tylonycteris bat coronavirus HKU4. These findings suggest that the increase in wildlife populations associated with urban greenspace development may pose a potential threat to human health that should not be overlooked.

Source: 

Link: https://www.mdpi.com/2076-2607/14/1/83

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