West African Clade C #MERS-CoV Strains BF785 and Mor213 Induce More Robust #Interferon and Inflammatory Signaling Compared to Clade A in #Human Respiratory Cells

 

Abstract

Clade A Middle East respiratory syndrome coronavirus (MERS-CoV) spilled over from camels into humans in Saudi Arabia in 2012 and caused pneumonia and severe respiratory disease, with a 37% case fatality rate. While clade A and B viruses are closely related phylogenetically, clade B MERS-CoV strains have since outcompeted clade A strains and continue to circulate in camels and humans in the Middle East and cause outbreaks in humans. Clade C strains circulate in camels across the African continent but have not been reported to cause disease in humans. We have shown that a number of East African clade C isolates are less able to utilize the TMPRSS2-mediated pathway for viral entry in both cell lines and primary nasal epithelial cultures, which may underlie the reduced replication of East African clade C strains in humans. However, the reduced replicative capacity of West African strains in human cells appears to be independent of viral entry, suggesting an alternative basis for their attenuation. Here, we report that West African clade C MERS-CoV isolates with deletions in ORF4b encoding a key accessory protein, NS4b, induced significantly more robust interferon and inflammatory responses than clade A MERS in human respiratory cell lines and primary bronchial air–liquid interface cultures. The replication deficit for the West African strain BF785, which has a complete deletion of ORF4b, was partially rescued when RNASEL was knocked out in A549 cells. These findings demonstrate that complete loss of NS4b results in stronger innate immune activation than partial truncation and suggests that differential selection on NS4b may contribute to the varying phenotypes of clade C MERS-CoV strains circulating in African camels.

Source: 

Link: https://www.mdpi.com/1999-4915/18/9/935

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#Risk #assessment of introduction, spread, and zoonotic #spillover of #MERS-CoV Clade B in #camel populations of the Nile Basin and Across #Africa (WHO, summary)

 

INTRODUCTION  

    The Global Early Warning System for Health Threats and Emerging Risks at the Human-Animal Ecosystems Interface (GLEWS+) is a joint initiative of the Food and Agriculture Organization of the UN (FAO), the World Health Organization (WHO), and the World Organisation for Animal Health (WOAH). 

    Within this framework, the GLEWS+ Risk Assessment (RA) mechanism enables the three organizations to jointly assess emerging health threats at the human–animal–ecosystem interface and provide evidence-based risk estimates. 

    These assessments support Members and State Parties in strengthening the prevention, detection, response and control measures.  

Event Description and Scope of the Assessment 

    Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus for which dromedary camels (Camelus dromedarius) are recognized as the primary animal reservoir. 

    Viral circulation within camel populations poses a risk of transmission to humans, particularly in settings characterized by frequent and close human–camel interactions. 

    Historically, MERS-CoV strains detected in dromedary camels in Africa have belonged to clade C, whereas clade B viruses have been associated with the majority of reported human MERS cases and have predominantly circulated in dromedary camel populations in the Middle East. 

    The recent detection of MERS-CoV clade B genome fragments in camels from the Nile Basin region represents a notable epidemiological development, suggesting the possibility of inter-regional viral movement and genetic mixing. 

    This finding may have implications for virus circulation and transmission dynamics, including potential changes in the risk of zoonotic spillover to humans and/or alterations in viral transmissibility and pathogenicity. 

    This assessment evaluates the risk of spread of MERS-CoV clade B within camel populations at both sub-regional (Nile Basin) and regional (Africa) levels. 

    It also assesses the risk of spillover from infected camels to humans in Nile Basin countries. 

    The assessment considers available virological, epidemiological, ecological, and socio-economic factors that influence virus circulation, including camel husbandry practices, pastoralist mobility patterns, cross-border animal movements, live-animal trade networks, and the extent of human-camel contact in the region.  

    Information used in this assessment was compiled from eight countries in Africa reporting camel populations exceeding 10,000 in 2024. 

    The countries included in the assessment are:     

        ° Chad, 

        ° Egypt*, 

        ° Eritrea*, 

        ° Ethiopia*, 

        ° Kenya*, 

        ° Libya, 

        ° South Sudan* and 

        ° Sudan*. 

    The six countries belonging to the Nile Basin sub-region are indicated by an asterisk (*). 

    This risk assessment reflects information available to 27 July 2026. FAO, WHO and WOAH will review and update the assessment as new information becomes available.  

SUMMARY 

    Middle East respiratory syndrome coronavirus (MERS-CoV) is an enveloped, positive-sense RNA virus belonging to the genus Betacoronavirus. 

    It causes Middle East respiratory syndrome (MERS), a zoonotic respiratory disease first recognized in 2012, following the detection of human cases in Saudi Arabia and Jordan. 

    As of 11 June 2026, a total of 2,637 laboratory-confirmed human cases have been reported to WHO globally, the majority from countries in the Arabian Peninsula, with an estimated crude case fatality ratio (CFR) of approximately 37%. (WHO, 2025c) 

    Dromedary camels (Camelus dromedarius) are the primary animal reservoir of MERS-CoV and the main source of zoonotic transmission to humans. 

    Human infections are thought to occur through direct or indirect contact with infected camels. 

    Consumption of raw camel products is considered a plausible route of exposure, although it has not been definitively confirmed as a primary transmission pathway. 

    Human-to-human transmission can occur, particularly in healthcare settings and among those in close-contact. 

    MERS-CoV antibodies have been found in other camelid species, including Bactrian camels, hybrid camels, llamas and alpacas, indicating susceptibility to infection (Islam, 2003). 

    However, these species are not considered to play a significant role in the current epidemiology of MERS.  

    MERS-CoV has evolved into three genetic clades (A, B, and C) with distinct geographic patterns. 

    Clade B predominates in the Arabian Peninsula and has been associated with all recent human infections. 

    Clade A has not been detected since 2015 and is considered extinct. 

    Clade C circulates among dromedary camels across Africa and despite frequent camel imports from Nile Basin countries into the Arabian Peninsula, has not become established in local camel populations. 

    Experimental and phenotypic studies indicate that clade B viruses exhibit higher replication efficiency in human respiratory tissues and experimentally infected camelids, more efficient cellular entry, and prolonged viral shedding compared with clade C viruses. (Rodon, 2023) 

    These characteristics suggest a greater zoonotic potential and an increased likelihood of transmission to humans. (Zhou, 2021) 

    The global camel population is estimated at over 42 million heads as of 2023, with more than 80% of the population in Africa (FAO, 2025a). 

    Camel trade within Africa is predominantly regional and fragmented, with significant informal cross-border movement. (WHO, 2025d, FAO, 2026) In the Nile Basin and the Horn of Africa {1}. 

    Camel trade and movement are largely driven by informal cross-border pastoralist systems, with frequent but poorly documented movements between neighboring countries such as Sudan, Ethiopia, Kenya, and South Sudan. 

    Sudan plays a central role as a major camel exporter, with substantial formal and informal movements to neighboring countries and toward North Africa, while Egypt functions primarily as a terminal hub where camels from multiple origins converge for trade and slaughter. 

    In contrast, long-distance east-to-west transcontinental movement appears limited, with little evidence of sustained camel movement from the Nile Basin into North or West Africa. (Younan et al., 2016) 

    Recent genomic surveillance studies have suggested the introduction of MERS-CoV clade B strains into camel populations in the Nile Basin, outside its historically recognized circulation in the Arabian Peninsula. 

    In Egypt, phylogenetic analyses of a camel-derived sample identified genome fragments clustering with clade B viruses from the Arabian Peninsula, circulating alongside endemic African clade C viruses (Gomaa, Edwards, Wang, Taweel, et al., 2025). 

    Recombination analyses in these studies were interpreted by the authors as suggesting potential genomic mixing between introduced clade B and endemic clade C lineages, highlighting a potential for inter-regional viral exchange and the emergence of novel variants. 

    However, as the publicly available sequences are incomplete, these findings require confirmation through full genome sequencing.  

    In a separate study (Hassan et al., 2025), metagenomic sequencing of nasal swabs from camels imported from Sudan also detected MERS-CoV genome fragments clustering with clade B human and camel strains. 

    Whole genome sequencing would be necessary to confirm these findings and better characterize their evolutionary relationships. 

    Overall, while these observations suggest the possible introduction of clade B viruses into camel population in the Nile Basin sub-region, additional research is required to determine whether there is sustained circulation, establishment, or recombination of clade B viruses in continental African camel populations. 

    Using a qualitative evidence-based approach and considering the assessed likelihood and consequences in the countries assessed, the overall risk at sub-regional level (Nile Basin) of further introduction and spread of MERS-CoV clade B within camel populations is minor. 

    The risk of introduction and spread from camel populations in the Nile Basin to camel populations in neighbouring countries is also assessed as minor. 

    However, if MERS-CoV clade B is introduced and established in camel populations in the Nile Basin countries, the public health risk of spillover from camels to humans exposed to infected camels or their products is assessed as high.  

    The level of confidence in the risk estimates is considered low for the first two questions, reflecting limitations in the quality and completeness of available genomic data, the presence of plausible but unconfirmed transmission pathways, very limited surveillance in camels and humans, and evolving camel trade dynamics that may facilitate virus spread within and beyond the Nile Basin. 

    The level of confidence is considered moderate for the third question. 

    While the clinical presentation and potential consequences of MERS-CoV infection in humans are well documented and observed in previous outbreaks, important uncertainties remain regarding the social, behavioral, and contextual factors that influence the likelihood of camel- to- human spillover in the Nile Basin.  

(...)

{1} Countries in the Horn of Africa are: Djibouti, Eritrea, Ethiopia, and Somalia

Source: 

Link: https://www.who.int/publications/m/item/risk-assessment-of-the-introduction--spread--and-zoonotic-spillover-of-mers-cov-clade-b-in-camel-populations-of-the-nile-basin-and-across-africa

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#Genomic and structural #evidence of #SARS-CoV-2 and #MERS-CoV in migratory #birds

 

Significance

Coronaviruses are regarded as highly important pathogens of birds and mammals. Herein, we obtained three almost full-length severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes and one partial Middle East respiratory syndrome coronavirus (MERS-CoV) genome in the feces of migratory birds based on meta-transcriptome and PCR amplification. We determined the affinities and the complex structures between receptor-binding domain (RBD) of the SARS-CoV-2 viral spike protein and angiotensin-converting enzyme 2 (ACE2) protein of two migratory birds, Tundra and Black swans. Moreover, pseudotyped SARS-CoV-2 variants can enter into HeLa cells expressing ACE2 proteins of these birds. Altogether, our results expand our understanding of migratory birds as potential carrier of both SARS-CoV-2 and MERS-CoV.

Abstract

Migratory birds are the natural reservoir of influenza A virus (IAV), but their role as a carrier of SARS-CoV-2 remains unclear. Here, we report the identification of three almost full-length viral genome sequences of SARS-CoV-2 variants of concern (VOCs) in Tundra swans. These sequences are named hCoV-19/Tundra swan/Jiangxi/IMCAS_M1/2021 (IMCAS_M1), hCoV-19/Tundra swan/Jiangxi /IMCAS_M2/2021 (IMCAS_M2), and hCoV-19/Tundra swan/Jiangxi/IMCAS_M3/2021 (IMCAS_M3). IMCAS_M1 and IMCAS_M3 have the same mutations as the Beta VOC (K417N, E484K, and N501Y) in the receptor-binding domain (RBD) of the viral spike (S) protein, whereas IMCAS_M2 shares the same mutations as the Gamma VOC (K417T, E484K, and N501Y) in the RBD with all three showing their distinct mutations in the genomes. Virus receptor angiotensin-converting enzyme 2 (ACE2) proteins from both Tundra swan (tsACE2) and Black swan (bsACE2) can bind to the RBDs of all three viruses and the Alpha VOC, but not to RBD of the prototype (PT) virus. The polar contacts and hydrophobic interactions revealed by cryo-electron microscopy (cryo-EM) structures of the RBD–ACE2 complex, play key roles in virus–receptor engagement. Furthermore, HeLa cells expressing bsACE2 and tsACE2 proteins could be transduced by pseudotyped SARS-CoV-2 variants (Alpha, Beta, and Gamma) but not PT SARS-CoV-2. In addition, we obtained one partial genome of MERS-CoV named Bar-headed goose/Tibet/IMCAS_M4/2022 (IMCAS_M4) with 20,180 bp (~70.0% coverage). Our findings highlight the importance of migratory birds as potential carrier of both SARS-CoV-2 and MERS-CoV, thereby posing potential threat to public health.

Source: 

Link: https://www.pnas.org/doi/abs/10.1073/pnas.2400023123?af=R

____

Evaluation of a proposed #link between the #SARS-CoV-2 #furin #cleavage site and mouse-adapted #MERS-coronavirus MA30

 

Significance

This study formally evaluates a hypothesis that has been advanced by some scientists and public commentators in support of a nonnatural origin of SARS-CoV-2. The hypothesis proposes that the unique polybasic furin cleavage motif of SARS-CoV-2 may be technically or evolutionarily derived from a mouse-adapted laboratory strain of MERS-coronavirus (MA30). While the World Health Organization’s Scientific Advisory Group on the Origins of Novel Pathogens (SAGO) concluded that the available evidence was insufficient to support the proposed link, the underlying scientific rationale for this conclusion has not been published. We systematically assessed the evidence from genomic surveillance and conducted additional experimental studies. Together, these data do not support an evolutionary or genetic relationship.

Abstract

The origin of the polybasic furin cleavage site (FCS) of SARS-CoV-2 remains a central question in debates on the emergence of COVID-19. One hypothesis proposes a genetic relationship between the SARS-CoV-2 S1/S2 motif RRAR and the RRVR sequence found in the mouse-adapted MERS-CoV strain MERS-MA30. Here, we combined large-scale bioinformatic analysis with experimental virology to evaluate this scenario. Analysis of over 17 million SARS-CoV-2 genomes revealed that the S:684V substitution corresponding to RRVR occurred repeatedly but only sporadically, never became phylogenetically basal, and showed limited geographic and temporal spread. Using reverse genetics, we generated SARS-CoV-2 variants encoding RRVR and demonstrated that S:684V consistently reduced viral entry efficiency and competitive fitness in multiple cell systems, including human respiratory epithelial cultures. RRVR variants did not evolve toward RRAR but instead accumulated alternative substitutions. These findings do not support an evolutionary relationship between MERS-MA30 and the SARS-CoV-2 FCS.

Source: 

Link: https://www.pnas.org/doi/abs/10.1073/pnas.2601806123?af=R

____

#Genomic and structural #evidence of #SARS-CoV-2 and #MERS-CoV in migratory #birds

 

Significance

Coronaviruses are regarded as highly important pathogens of birds and mammals. Herein, we obtained three almost full-length severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes and one partial Middle East respiratory syndrome coronavirus (MERS-CoV) genome in the feces of migratory birds based on meta-transcriptome and PCR amplification. We determined the affinities and the complex structures between receptor-binding domain (RBD) of the SARS-CoV-2 viral spike protein and angiotensin-converting enzyme 2 (ACE2) protein of two migratory birds, Tundra and Black swans. Moreover, pseudotyped SARS-CoV-2 variants can enter into HeLa cells expressing ACE2 proteins of these birds. Altogether, our results expand our understanding of migratory birds as potential carrier of both SARS-CoV-2 and MERS-CoV.

Abstract

Migratory birds are the natural reservoir of influenza A virus (IAV), but their role as a carrier of SARS-CoV-2 remains unclear. Here, we report the identification of three almost full-length viral genome sequences of SARS-CoV-2 variants of concern (VOCs) in Tundra swans. These sequences are named hCoV-19/Tundra swan/Jiangxi/IMCAS_M1/2021 (IMCAS_M1), hCoV-19/Tundra swan/Jiangxi /IMCAS_M2/2021 (IMCAS_M2), and hCoV-19/Tundra swan/Jiangxi/IMCAS_M3/2021 (IMCAS_M3). IMCAS_M1 and IMCAS_M3 have the same mutations as the Beta VOC (K417N, E484K, and N501Y) in the receptor-binding domain (RBD) of the viral spike (S) protein, whereas IMCAS_M2 shares the same mutations as the Gamma VOC (K417T, E484K, and N501Y) in the RBD with all three showing their distinct mutations in the genomes. Virus receptor angiotensin-converting enzyme 2 (ACE2) proteins from both Tundra swan (tsACE2) and Black swan (bsACE2) can bind to the RBDs of all three viruses and the Alpha VOC, but not to RBD of the prototype (PT) virus. The polar contacts and hydrophobic interactions revealed by cryo-electron microscopy (cryo-EM) structures of the RBD–ACE2 complex, play key roles in virus–receptor engagement. Furthermore, HeLa cells expressing bsACE2 and tsACE2 proteins could be transduced by pseudotyped SARS-CoV-2 variants (Alpha, Beta, and Gamma) but not PT SARS-CoV-2. In addition, we obtained one partial genome of MERS-CoV named Bar-headed goose/Tibet/IMCAS_M4/2022 (IMCAS_M4) with 20,180 bp (~70.0% coverage). Our findings highlight the importance of migratory birds as potential carrier of both SARS-CoV-2 and MERS-CoV, thereby posing potential threat to public health.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/

Link: https://www.pnas.org/doi/10.1073/pnas.2400023123

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Addressing the #zoonotic #threat of #merbecoviruses

 

Abstract

Merbecovirus is a subgenus of betacoronaviruses and exhibits high genetic diversity with a capacity for cross-species transmission. However, beyond Middle East respiratory syndrome coronavirus (MERS-CoV), our knowledge of the ecology and pathogenic potential of these viruses remains limited. Merbecoviruses were once thought to rely exclusively on dipeptidyl peptidase 4 for cell entry, but recent discoveries have revealed that several members can also engage with angiotensin-converting enzyme 2 or aminopeptidase N, expanding their receptor repertoire and potential host range. Here we summarize recent advances in understanding of the receptor usage of merbecoviruses and examine how these insights inform pandemic preparedness and risk assessment. We discuss the development of targeted diagnostics, broad-spectrum antivirals and vaccines, including pan-coronavirus strategies. Together, these advances provide a foundation for predictive surveillance and rational countermeasure design, enabling earlier detection and more effective containment of future merbecovirus spillover events before they escalate into epidemics.

Source: 

Link: https://www.nature.com/articles/s41564-026-02397-1

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#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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Sequencing of #Betacoronavirus erinacei from faeces of pet #hedgehogs demonstrates a continuity of #MERS-CoV like viruses in #European and Eurasian hedgehog species

 

Abstract

Hedgehogs have been recently identified as carriers of Betacoronavirus erinacei (also known as Erinaceus coronavirus, EriCoV) a virus closely related to B. cameli responsible for human Middle East Respiratory Syndrome (MERS), raising questions about the risk of hedgehog-to-human transmission and suggesting the need for coronavirus (CoV) surveillance in hedgehogs. This study investigated the presence of CoVs in fecal samples of hedgehogs kept as pets in Italy in 2021–2022. A pan-CoV nested RT-PCR targeting the RdRp gene was used for screening and positive samples were sequenced and phylogenetically analyzed. Two (6.2%) out of 30 hedgehogs analyzed were positive for B. erinacei represented by 2/3 (66.7%) long eared hedgehog (Hemiechinus auritus) while all the 27 tested African pygmy hedgehog (Atelerix albiventris) were negative. Whole genome sequence obtained from one B. erinacei-positive sample showed closest homology (85.7%) with B. erinacei previously detected in Erinaceus sp. from Eastern Russia. Phylogeny showed that the virus of this study formed a separate clade in the cluster with other B. erinacei identified in Europe and European Russia and did not cluster with other B. erinacei identified in China in Amur hedgehog (E. amurensis). No recombination events were observed. Analysis of the Spike protein revealed the presence of six out of the 11 key receptor binding residues, including two out of the three critical residues recently identified for the binding of Erinaceus europaeus receptor APN and B. erinacei. Results of this study suggest the presence of a long-eared hedgehog-specific strain of B. erinacei. Overall results support the circulation of coronaviruses along a phylogenetic continuum among different species of hedgehogs and geographic locations, suggesting the need for further CoV surveillance in both domestic and wild animals. There is also a need for studies on the affinity of EriCoV with the H. auritus APN specific receptor to confirm its involvement in the viral entry process.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S2352771426000960?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

____

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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Detection of a #Merbecovirus with potential #ACE2 usage in #France

 

ABSTRACT

A novel Merbecovirus, designated Cam-2023, has been identified in Pipistrellus pipistrellus in France through non-invasive surveillance. Phylogenetic analysis demonstrates that Cam-2023 belongs to a Merbecovirus clade previously associated with ACE2 usage in closely related viruses detected in the Netherlands and Russia. While the receptor usage of Cam-2023 remains to be functionally validated, sequence similarities within the Spike protein, particularly the receptor-binding domain, suggest a putative association with a Merbecovirus clade previously associated with ACE2 usage. This discovery broadens the known host diversity of this lineage and extends its geographical range to Western Europe. Our findings highlight the importance of continuous surveillance in European bat populations to better characterize the distribution and zoonotic potential of such high-risk coronaviruses.

Source: 

Link: https://www.tandfonline.com/doi/full/10.1080/22221751.2026.2651469

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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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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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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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