The MERS-COV virus is a zoonotic coronavirus that emerged in 2012 in KSA and caused viral illness with a case fatality rate up to 35 %. Over a decade later, the virus is still evolving and circulating. The aim of this review is to discuss the current epidemiology of MERS-COV both in humans and animals, during and post the COVID-19 pandemic. We have found that MERS-COV is still evolving in camels with new lineages being detected in Saudi Arabia. Although the number of human cases has decreased, there is a gradual resurgence in the number of cases. Furthermore, many cases are being reported without exposure to camels and/or raw products, nor contact with known human cases. This necessitates global efforts in the surveillance of asymptomatic carriers in the community, role of unknown animal reservoirs in the virus spread if any, as well as extensive genomic surveillance of the virus. This is in order to unveil and assess the genetic changes that the virus is undergoing and their according effect on the viral fitness, tropism, and virulence. These efforts are crucial for potential future pandemic preparedness, understanding the modes of transmission, as well as drug and vaccine development for MERS-COV.
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.
Respiratory syncytial virus is among the most common viruses causing respiratory infections in children. It has been suggested that imbalance of the respiratory microbiota could be involved in the prognosis of RSV illness. The aim of this work is to explore dysbiosis of nasal/anal microbiota in children upon RSV infection, compared to controls. Fifty-nine subjects were enrolled in this study and included: 23 controls, 17 infected only with RSV, and 19 RSV infected together with other respiratory viruses. Multi-infected subjects had non-statistically significant, higher rates of ICU admission (8 versus 3), oxygen supplementation (13 versus 9), and longer hospital stay (20 versus 15 mean days), compared to those single infected with RSV (P > 0.05). Meta-transcriptomic analysis revealed that the nasal microbiota of multi-infected RSV patients had significantly lower alpha richness compared to RSV mono-infected and control group. Principal component analysis revealed the distinct clustering of the nasal microbiome based on the infectious category (P < 0.05). Following the control of confounders i.e. age, gender, comorbidities and antimicrobial intake, Pseudomonas were significantly increased in RSV patients compared to controls. Lactobacillus, Bacteroides, and Staphylococcus were significantly decreased in multi-infected compared to the control subjects. For the anal microbiota, multi-RSV-infected patients had significantly lower alpha richness according to the observed indices, when compared only to the control group. RSV patients had both significantly lower abundance of Spirochaetes and Actinobacteria compared to the control group (P < 0.05). However, following the control of confounders, no significant difference was observed (P > 0.05). Our study revealed that multi-infected RSV subjects revealed the highest difference in microbial composition of the nasal microbiota compared to single infected and control subjects. Whether the observed microbiome difference is related to increased disease severity is yet to be explored in future studies. Moreover, the potential use of Lactobacillus and Bacteroides as probiotics for the treatment and prevention of RSV infection should be explored in future research.
Background/Objectives: SARS-CoV-2 is one of the viruses that caused worldwide health issues. This effect is mainly due to the wide range of disease prognoses it can cause. The aim of this study is to determine protein profiles that can be used as potential biomarkers for patients’ stratification, as well as potential targets for drug development. Methods: Eighty peripheral blood samples were collected from heathy as well as SARS-CoV-2 patients admitted at a major tertiary care center in Riyadh, Saudi Arabia. A label-free quantitative mass spectrometry-based proteomic analysis was conducted on the extracted sera. Protein–protein interactions and functional annotations of identified proteins were performed using the STRING. Results: In total, two-hundred-eighty-eight proteins were dysregulated among all four categories. Dysregulated proteins were mainly involved in the network map of SARS-CoV-2, immune responses, complement activation, and lipid transport. Compared to healthy subjects, the most common upregulated protein in all three categories were CRP, LGALS3BP, SAA2, as well as others involved in SARS-CoV-2 pathways such as ZAP70 and IGLL1. Notably, we found fifteen proteins that significantly discriminate between healthy/recovered subjects and moderate/under medication patients, among which are the SERPINA7, HSPD1 and TTC41P proteins. These proteins were also significantly downregulated in under medication versus moderate patients. Conclusions: Our results emphasize the possible association of specific proteins with the SARS-CoV-2 pathogenesis and their potential use as disease biomarkers and drug targets. Our study also gave insights about specific proteins that are likely increased upon infection but are likely restored post recovery.