SARS-CoV and MERS-CoV are two coronaviruses that have received significant attention due to their high pathogenicity and mortality rates in human populations. In this study, we compared their evolutionary dynamics to provide a One Health perspective on their differences in terms of the results of disease control. The phylogenetic network of SARS-CoVs showed that human isolates gathered into a “super-spreader” cluster and were distinct from civet isolates. In contrast, dromedary camel- and human-isolated MERS-CoVs were clustered together. Thus, most clades of MERS-CoV can infect humans, and MERS-CoVs seem to more easily spill over the animal-to-human interface. Additionally, the civet can be easily controlled, while the intermediate host (dromedary camels) of MERS-CoV is an important livestock species, so it is impossible to eliminate all animals. This further leads to difficulties in disease control in MERS. Although MERS-CoVs are endemic to dromedary camels in both the Middle East and Africa, human infections are mainly linked to the Middle East. The nucleotide sequences of the MERS-CoV receptor gen (dipeptidyl peptidase 4 (DPP4)) from 30 Egyptians, 36 Sudanese, and 34 Saudi Arabians showed little difference. These findings suggest that the observed disparities in MERS prevalence between populations in the Middle East and Africa may be more strongly attributed to inadequate disease surveillance and the limited camel-to-human transmission of clade C MERS-CoV in Africa, rather than variations in DPP4 gene.

SARS-CoV and MERS-CoV are two coronaviruses that received great attention due to their high pathogenicity and mortality rates in human populations. In this study, we compared their evolutionary dynamics to provide a One Health perspective of their different results of disease control. The phylogenetic network of SARS-CoVs showed that human isolates gathered into a “super-spreader” cluster, and were distinct from civet isolates. In contrast, dromedary camel- and human-isolated MERS-CoVs were clustered together. Thus, most clades of MERS-CoV can infect humans, and MERS-CoVs seem easier to spill over from animal-to-human interface. Additionally, the civet can be easily controlled, while the intermediate host (dromedary camels) of MERS-CoV is important livestock, so it is impossible to eliminate all animals. This further leads to difficulties in disease control of MERS. Although MERS-CoVs are endemic to dromedary camels in both the Middle East and Africa, human infections are mainly linked to the Middle East. The nucleotide sequences of the MERS-CoV receptor gene--dipeptidyl peptidase 4 (DPP4) from 30 Egyptians, 36 Sudanese, and 34 Saudi Arabians showed little difference. These findings suggest that the observed disparities in MERS prevalence between populations in the Middle East and Africa may be attributed more to inadequate disease surveillance and the limited camel-to-human transmission of clade C MERS-CoV in Africa, rather than variations in DPP4 gene.

Kobuviruses are emerging enteric pathogens with broad host ranges, yet their pathogenic potential in wild large felids remains largely unexplored. Here, we report the first case of fatal systemic infection caused by a novel Aichivirus A (AiV-A) strain, designated FeKoV0813, in a captive juvenile white lion (Panthera leo). The animal presented with acute respiratory distress and severe diarrhea, culminating in death despite supportive care. Comprehensive diagnostic workflows, including necropsy, histopathology, fluorescence in situ hybridization (FISH), and absolute quantitative RT-PCR, were employed to determine tissue tropism and viral dissemination. Whole-genome sequencing, phylogenetic analysis, and selection pressure assessment were conducted to characterize the viral evolutionary dynamics and host-specific constraints. The 8,213-nucleotide genome exhibited typical Kobuvirus organization, clustering within the Aichivirus A clade alongside carnivore-derived strains from dogs, cats, and foxes. High viral RNA loads were detected primarily in the small intestine (~7.4 log₁₀ copies/100 ng RNA) and trachea, with dissemination to the kidney and pancreas. Histopathological and FISH analyses localized viral RNA to epithelial lesions, while transcriptomic profiling revealed a robust upregulation of pro-inflammatory cytokines (particularly CXCL8) in the heavily infected intestine. Notably, selection pressure analysis indicated strong purifying selection acting on the feline VP1 gene, with no positively selected sites identified, contrasting with signatures of episodic positive selection observed in human and rodent lineages. This study provides the first definitive evidence that AiV-A can act as a fatal systemic pathogen in a large felid, significantly expanding the known host range of kobuviruses. Our findings underscore the need for vigilant surveillance of kobuviruses in captive wildlife and highlight the potential risk of spillover infections from domestic carnivore reservoirs.

Kobuviruses are emerging enteric pathogens with broad host ranges, yet their pathogenic potential in wild large felids remains largely unexplored. Here, we report the first case of severe enteric and respiratory disease associated with AiV-A infection in a large felid, designated FeKoV0813, in a captive juvenile white lion (Panthera leo). The animal presented with acute respiratory distress and severe diarrhea, culminating in death despite supportive care. Comprehensive diagnostic workflows, including necropsy, histopathology, fluorescence in situ hybridization (FISH), and absolute quantitative RT-PCR, were employed to determine tissue tropism and viral dissemination. Whole-genome sequencing, phylogenetic analysis, and selection pressure assessment were conducted to characterize the viral evolutionary dynamics and host-specific constraints. The 8213-nucleotide genome exhibited typical Kobuvirus organization, clustering within the AiV-A clade alongside carnivore-derived strains from dogs, cats, and foxes. High viral RNA loads were detected primarily in the small intestine (~7.4 log₁₀ copies/100 ng RNA) and trachea, with dissemination to the kidney and pancreas. Histopathological analysis revealed epithelial lesions, and FISH localized viral RNA to these affected epithelial cells, while transcriptomic profiling revealed higher transcript abundance of CXCL8 and other pro-inflammatory genes in the intestine than in other tissues. Notably, selection pressure analysis indicated strong purifying selection acting on the feline VP1 gene, with no positively selected sites identified, contrasting with signatures of episodic positive selection observed in human and rodent lineages. This study provides the first report of severe respiratory and gastrointestinal disease associated with AiV-A infection in large felids, significantly expanding the known host range of kobuviruses. Our findings underscore the need for vigilant surveillance of kobuviruses in captive wildlife and highlight the potential risk of spillover infections from domestic carnivore reservoirs.