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Background: Middle East Respiratory Syndrome (MERS) has become a severe zoonotic disease, posing significant public health concerns due to the lack of specific medications. This urgently demands the development of novel therapeutic molecules. Understanding MERS's genetic underpinnings and potential therapeutic targets is crucial for developing effective treatments. Methods: Two gene expression datasets (GSE81909 and GSE100504) were analyzed to identify differentially expressed genes (DEGs) using GEO2R. Furthermore, gene ontology (GO), pathway enrichment analysis, and protein-protein interaction (PPI) network were performed to understand the gene’s functions. A possible drug target was identified, and an FDA-approved drug library was screened against the selected target using molecular docking and validated the findings through molecular dynamics simulation, principal component analysis, free energy landscape, and MM/GBSA calculations. Results: The study on GSE81909 and GSE100504 datasets with icMERS and MOCK samples at 24 and 48 h revealed an upregulation in 73 and 267 DEGs, respectively. In the network pharmacology, STAT1, MX1, DDX58, EIF2AK2, ISG15, IFIT1, IFIH1, OAS1, IRF9, and OASL were identified as the top 10 hub genes. STAT1 was identified as the most connected hub gene among these top 10 hub genes, which plays a crucial role in the immune response to the MERS virus. Further study on STAT1 showed that PPARG helps reduce STAT1, which could modulate the immune response. Therefore, by inhibiting PPARG, the immunological response can be successfully enhanced. The known inhibitor of PPARG, 570 (Farglitazar), was used as a control. Further, screening using Tanimoto and K-mean clustering was performed, from which three compounds were identified: 2267, 3478, and 40326. Compound 3478 showed characteristics similar to the control, indicating robust binding to PPARG. 3478 showed the highest negative binding free energy with −41.20 kcal/mol, indicating strong binding with PPARG. Conclusions: These findings suggest that 3478 promises to be a potential inhibitor of PPARG, and further experimental investigations can explore its potential as a MERS inhibitor.

The emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has posed a significant global health concern due to its severe respiratory illness and high fatality rate. Currently, despite the potential for resurgence, there are no specific treatments for MERS-CoV, and only supportive care is available. Our study aimed to address this therapeutic gap by developing a potent neutralizing bispecific antibody (bsAb) against MERS-CoV. Initially, we isolated four human monoclonal antibodies (mAbs) that specifically target the MERS-CoV receptor-binding domain (RBD) using phage display technology and an established human antibody library. Among these four selected mAbs, our intensive in vitro functional analyses showed that the MERS-CoV RBD-specific mAb K111.3 exhibited the most potent neutralizing activity against MERS-CoV pseudoviral infection and the molecular interaction between MERS-CoV RBD and human dipeptidyl peptidase 4. Consequently, we engineered a novel bsAb, K207.C, by utilizing K111.3 as the IgG base and fusing it with the single-chain variable fragment of its non-competing pair, K111.1. This engineered bsAb showed significantly enhanced neutralization potential against MERS-CoV compared to its parental mAb. These findings suggest that K207.C may serve as a potential candidate for effective MERS-CoV neutralization, further highlighting the promise of the bsAb dual-targeting approach in MERS-CoV neutralization.

The Middle East respiratory syndrome (MERS) is a severe respiratory disease with high fatality rates, caused by the Middle East respiratory syndrome coronavirus (MERS-CoV). The virus initiates infection by binding to the CD26 receptor (also known as dipeptidyl peptidase 4 or DPP4) via its spike protein. Although the receptor-binding domain (RBD) of the viral spike protein and the complex between RBD and the extracellular domain of CD26 have been studied using X-ray crystallography, conflicting studies exist regarding the importance of certain amino acids outside the resolved RBD-CD26 complex interaction interface. To gain atomic-level knowledge of the RBD-CD26 complex, we employed computational simulations to study the complex's dynamic behavior as it evolves from its crystal structure to a conformation stable in solution. Our study revealed previously unidentified interaction regions and interacting amino acids within the complex, determined a novel comprehensive RBD-binding domain of CD26, and by that expanded the current understanding of its structure. Additionally, we examined the impact of a single amino acid substitution, E513A, on the complex's stability. We discovered that this substitution disrupts the complex through an allosteric domino-like mechanism that affects other residues. Since MERS-CoV is a zoonotic virus, we evaluated its potential risk of human infection via animals, and suggest a low likelihood for possible infection by cats or dogs. The molecular structural information gleaned from our insights into the RBD-CD26 complex pre-dissociative states may be proved useful not only from a mechanistic view but also in assessing inter-species transmission and in developing anti-MERS-CoV antiviral therapeutics.

Concerns about the social and economic collapse, high mortality rates, and stress on the healthcare system are developing due to the coronavirus onslaught in the form of various species and their variants. In the recent past, infections brought on by coronaviruses severe acute respiratory syndrome coronaviruses (SARS-CoV and SARS-CoV-2) as well as middle east respiratory syndrome coronavirus (MERS-CoV) have been reported. There is a severe lack of medications to treat various coronavirus types including MERS-CoV which is hazard to public health due to its ability for pandemic spread by human-to-human transmission. Here, we utilized sinapic acid (SA) against papain-like protease (PLpro), a crucial enzyme involved in MERS-CoV replication, because phytomedicine derived from nature has less well-known negative effects. The thermal shift assay (TSA) was used in the current study to determine whether the drug interact with the recombinant MERS-CoV PLpro. Also, inhibition assay was conducted as the hydrolysis of fluorogenic peptide from the Z-RLRGG-AMC-peptide bond in the presence of SA to determine the level of inhibition of the MERS-CoV PLpro. To study the structural binding efficiency Autodock Vina was used to dock SA to the MERS-CoV PLpro and results were analyzed using PyMOL and Maestro Schrödinger programs. Our results show a convincing interaction between SA and the MERS protease, as SA reduced MERS-CoV PLpro in a dose-dependent way IC50 values of 68.58 μM (of SA). The TSA showed SA raised temperature of melting to 54.61 °C near IC50 and at approximately 2X IC50 concentration (111.5 μM) the Tm for SA + MERS-CoV PLpro was 59.72 °C. SA was docked to MERS-CoV PLpro to identify the binding site. SA bound to the blocking loop (BL2) region of MERS-CoV PLpro interacts with F268, E272, V275, and P249 residues of MERS-CoV PLpro. The effectiveness of protease inhibitors against MERS-CoV has been established and SA is already known for broad range biological activity including antiviral properties; it can be a suitable candidate for anti-MERS-CoV treatment.

Objectives: The World Health Organization priority zoonotic pathogen Middle East respiratory syndrome (MERS) coronavirus (CoV) has a high case fatality rate in humans and circulates in camels worldwide. Methods: We performed a global analysis of human and camel MERS-CoV infections, epidemiology, genomic sequences, clades, lineages, and geographical origins for the period January 1, 2012 to August 3, 2022. MERS-CoV Surface gene sequences (4061 bp) were extracted from GenBank, and a phylogenetic maximum likelihood tree was constructed. Results: As of August 2022, 2591 human MERS cases from 26 countries were reported to the World Health Organization (Saudi Arabia, 2184 cases, including 813 deaths [case fatality rate: 37.2%]) Although declining in numbers, MERS cases continue to be reported from the Middle East. A total of 728 MERS-CoV genomes were identified (the largest numbers were from Saudi Arabia [222: human = 146, camels = 76] and the United Arab Emirates [176: human = 21, camels = 155]). A total of 501 ‘S’-gene sequences were used for phylogenetic tree construction (camels [n = 264], humans [n = 226], bats [n = 8], other [n=3]). Three MERS-CoV clades were identified: clade B, which is the largest, followed by clade A and clade C. Of the 462 clade B lineages, lineage 5 was predominant (n = 177). Conclusion: MERS-CoV remains a threat to global health security. MERS-CoV variants continue circulating in humans and camels. The recombination rates indicate co-infections with different MERS-CoV lineages. Proactive surveillance of MERS-CoV infections and variants of concern in camels and humans worldwide, and development of a MERS vaccine, are essential for epidemic preparedness.

A deadly respiratory disease Middle East Respiratory Syndrome (MERS) is caused by a perilous virus known as MERS-CoV, which has a severe impact on human health. Currently, there is no approved vaccine, prophylaxis, or antiviral therapeutics for preventing MERS-CoV infection. Due to its inexorable and integral role in the maturation and replication of the MERS-CoV virus, the 3C-like protease is unavoidly a viable therapeutic target. In this study, 2369 phytoconstituents were enlisted from Japanese medicinal plants, and these compounds were screened against 3C-like protease to identify feasible inhibitors. The best three compounds were identified as Kihadanin B, Robustaflavone, and 3-beta-O- (trans-p-Coumaroyl) maslinic acid, with binding energies of −9.8, −9.4, and −9.2 kcal/mol, respectively. The top three potential candidates interacted with several active site residues in the targeted protein, including Cys145, Met168, Glu169, Ala171, and Gln192. The best three compounds were assessed by in silico technique to determine their drug-likeness properties, and they exhibited the least harmful features and the greatest drug-like qualities. Various descriptors, such as solvent-accessible surface area, root-mean-square fluctuation, root-mean-square deviation, hydrogen bond, and radius of gyration, validated the stability and firmness of the protein-ligand complexes throughout the 100ns molecular dynamics simulation. Moreover, the top three compounds exhibited better binding energy along with better stability and firmness than the inhibitor (Nafamostat), which was further confirmed by the binding free energy calculation. Therefore, this computational investigation could aid in the development of efficient therapeutics for life-threatening MERS-CoV infections.

Middle East respiratory syndrome coronavirus (MERS-CoV), a highly pathogenic coronavirus in the same Betacoronavirus genus and Coronaviridae family as SARS-CoV-2, continues to post a threat to human health. Mortality remains high; therefore, there is a need to develop effective vaccines to prevent MERS-CoV infection. The receptor-binding domain (RBD) within the MERS-CoV spike (S) protein is a critical vaccine target. The latest mRNA technology has enabled rapid development of much-needed vaccines with high efficiency and scalable manufacturing capacity. Here, we designed a mRNA vaccine encoding the RBD of MERS-CoV S protein (RBD-mRNA) and evaluated its immunogenicity and protective efficacy in a mouse model. The data showed that nucleoside-modified RBD-mRNA, but not RBD-mRNA lacking the nucleoside modification, was stable and elicited broadly and durable neutralizing antibody and cellular immune responses, which neutralized the original strain and multiple MERS-CoV variants. Among all immunization routes tested, the intradermal route was appropriate for this RBD-mRNA to induce strong B-cell responses and the highest neutralizing antibody titers. Importantly, injection of nucleoside-modified RBD-mRNA through the intradermal route protected immunized mice against challenge with MERS-CoV. This protection correlated with serum neutralizing antibody titers. Overall, we have developed an effective MERS-CoV RBD-based mRNA vaccine (with potential for further development) that prevents infection by divergent strains of MERS-CoV.

Background: Middle East respiratory syndrome-coronavirus (MERS-CoV) utilizes CD26 (dipeptidyl peptidase‐4) and CD66e or CEACAM5 (carcinoembryonic antigen-related cell adhesion molecule 5) receptors for cell infection. Peripheral blood mononuclear cells (PBMCs) play a critical role in mounting adaptive immune response against the virus. This study was performed to assess the expression of CD26 and CD66e on PBMCs and their susceptibility to MERS-CoV infection. Methods: Surface expression of CD26 and CD66e receptors on PBMCs from MERS-CoV patients (n = 20) and healthy controls (n = 20) was assessed by flow cytometry and the soluble forms were determined by enzyme-linked immunosorbent assay (ELISA). MERS-CoV UpE and Orf1a genes in PBMCs were detected by using Altona diagnostics reverse transcription polymerase chain reaction (RT-PCR) kit. Results: Mean fluorescent intensity (MFI) of CD66e was significantly higher on CD4 + lymphocytes (462.4 ± 64.35 vs 325.1 ± 19.69; p

The Middle East respiratory syndrome Coronavirus (MERS-CoV) is one of the human coronaviruses that causes severe respiratory infection. Bats are considered to be the natural reservoir, where dromedary camels (DC) are the intermediate hosts of the virus. The current study was undertaken to provide an update on global distribution of the virus in camels, and to investigate the pooled prevalence and camel-associated risk factors of infection. After registration of the review protocol in the Open Science Framework, data searches were conducted on 18 April 2023 through Embase, PubMed, Scopus, and Web of Science. Considering only natural MERS-CoV infection in camels, 94 articles were selected for data curation through blind screening by two authors. Meta-analysis was conducted to estimate the pooled prevalence and to evaluate camel-associated risk factors. Finally, the results were presented in forest plots. The reviewed articles tested 34 countries, of which camels of 24 countries were seropositive and in 15 countries they were positive by molecular method. Viral RNA was detected in DC. Non-DC, such as bactrian camels, alpaca, llama, and hybrid camels were only seropositive. The global estimated pooled seroprevalence and viral RNA prevalence in DC were 77.53% and 23.63%, respectively, with the highest prevalence in West Asia (86.04% and 32.37% respectively). In addition, 41.08% of non-DC were seropositive. The estimated pooled prevalence of MERS-CoV RNA significantly varied by sample types with the highest in oral (45.01%) and lowest in rectal (8.42%) samples; the estimated pooled prevalence in nasal (23.10%) and milk (21.21%) samples were comparable. The estimated pooled seroprevalence in 5 years age groups were 56.32%, 75.31%, and 86.31%, respectively, while viral RNA prevalence was 33.40%, 15.87%, and 13.74%, respectively. Seroprevalence and viral RNA prevalence were generally higher in females (75.28% and 19.70%, respectively) than in males (69.53% and 18.99%, respectively). Local camels had lower estimated pooled seroprevalence (63.34%) and viral RNA prevalence (17.78%) than those of imported camels (89.17% and 29.41%, respectively). The estimated pooled seroprevalence was higher in camels of free-herds (71.70%) than confined herds (47.77%). Furthermore, estimated pooled seroprevalence was higher in samples from livestock markets, followed by abattoirs, quarantine, and farms but viral RNA prevalence was the highest in samples from abattoirs, followed by livestock markets, quarantine, and farms. Risk factors, such as sample type, young age, female sex, imported camels, and camel management must be considered to control and prevent the spread and emergence of MERS-CoV.

Background: A new coronavirus was identified in Jeddah, Saudi Arabia in 2012 and designated as Middle East Respiratory Syndrome Coronavirus (MERS-CoV). To date, this virus has been reported in 27 countries. The virus transmission to humans has already been reported from camels. Currently, there is no vaccine or antiviral therapy available against this virus. Methods: The siRNAs were in silico predicted, designed, and chemically synthesized by using the MERS-CoV-orf1ab region as a target. The antiviral activity was experimentally evaluated by delivering the siRNAs with Lipofectamine™ 2000 and JetPRIMER as transfection reagents in both Vero cell and HEK-293-T cell lines at two different concentrations (10.0 nM and 5.0 nM). The Ct value of quantitative Real-Time PCR (qRT-PCR) was used to calculate and determine the reduction of viral RNA level in both cell supernatant and cell lysate isolated from both cell lines. Results: The sequence alignment resulted in the selection of highly conserved regions. The orf1ab region was used to predict and design the siRNAs and a total of twenty-one siRNAs were finally selected from four hundred and twenty-six siRNAs generated by online software. Inhibition of viral replication and significant reduction of viral RNA was observed against selected siRNAs in both cell lines at both concentrations. Based on the Ct value, the siRNAs # 11, 12, 18, and 20 were observed to be the best performing in both cell lines at both concentrations. Conclusion: Based on the results and data analysis, it is concluded that the use of two different transfection reagents was significantly effective. But the Lipofectamine™ 2000 was found to be a better transfection reagent than the JetPRIMER for the delivery of siRNAs in both cell lines.

Coronaviruses (CoVs) have the largest genome among RNA viruses and store large amounts of information without genome integration as they replicate in the cell cytoplasm. The replication of the virus is a continuous process, whereas the transcription of the subgenomic mRNAs is a discontinuous one, involving a template switch, which resembles a high frequency recombination mechanism that may favor virus genome variability. The origin of the three deadly human CoVs SARS-CoV, MERS-CoV and SARS-CoV-2 are zoonotic events. SARS-CoV-2 has incorporated in its spike protein a furine proteolytic site that facilitates the activation of the virus in any tissue, making this CoV strain highly polytropic and pathogenic. Using MERS-CoV as a model, a propagation-deficient RNA replicon was generated by removing E protein gene (essential for viral morphogenesis and involved in virulence), and accessory genes 3, 4a, 4b and 5 (responsible for antagonism of the innate immune response) to attenuate the virus: MERS-CoV-Δ[3,4a,4b,5,E]. This RNA replicon is strongly attenuated and elicits sterilizing protection after a single immunization in transgenic mice with the receptor for MERS-CoV, making it a promising vaccine candidate for this virus and an interesting platform for vector-based vaccine development. A strategy could be developed for the design of RNA replicon vaccines for other human pathogenic coronaviruses.

Since the end of 2019, the outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has triggered a pneumonia epidemic, posing a significant public health challenge in 236 countries, territories, and regions worldwide. Clinically, in addition to the symptoms of pulmonary infection, many patients with SARS-CoV-2 infections, especially those with a critical illness, eventually develop multiple organ failure in which damage to the kidney function is common, ultimately leading to severe consequences such as increased mortality and morbidity. To date, three coronaviruses have set off major global public health security incidents: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and SARS-CoV-2. Among the diseases caused by the coronaviruses, the coronavirus disease 2019 (COVID-19) has been the most impactful and harmful. Similar to with SARS-CoV-2 infections, previous studies have shown that kidney injury is also common and prominent in patients with the two other highly pathogenic coronaviruses. Therefore, in this review, we aimed to comprehensively summarize the epidemiological and clinical characteristics of these three pandemic-level infections, provide a deep analysis of the potential mechanism of COVID-19 in various types of kidney diseases, and explore the causes of secondary kidney diseases of SARS-CoV-2, so as to provide a reference for further research and the clinical prevention of kidney damage caused by coronaviruses.

The zoonotic Middle East respiratory syndrome (MERS) is caused by an emerging beta-coronavirus (CoV). The majority of MERS studies have included scattered data from sub-Saharan Africa and the Middle East, and these data have not been analyzed collectively. In this work, a meta-analysis of these studies was conducted to coalesce these results, determine the prevalence and seroprevalence of MERS-CoV in camels and humans, and examine how zoonotic infection rates in dromedary camels are related to human infection rates. After extracting the collected data, the prevalence and seroprevalence at a 95% confidence interval (CI) using a fixed-effects inverse-variance meta-analysis was conducted. Thirteen studies were included. Eight studies included 2905 samples from dromedary camels, of which 1108 (38.14%) were positive for the virus. The prevalence was 8.75[−13.47, 30.98] at 95% CI in dromedary camels and 0.03[−35.23, 35.28] at 95% CI in humans. Ten studies included 7176 serum samples, 5788 (80.66%) of which were positive. The seroprevalence was 20.69[−4.60, 45.99] at 95% CI. The prevalence of MERS-CoV was moderate to high, but the seroprevalence was high. Despite the high prevalence of the virus in camel herds, zoonotic transmissions were not widespread. Further longitudinal and cross-sectional follow-up studies are recommended to provide solid control of MERS-CoV transmission.

Recurrent epidemics of coronaviruses have posed significant threats to human life and health. The mortality rate of patients infected with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is 35 %. The main protease (M pro ) plays a crucial role in the MERS-CoV life cycle, and M pro exhibited a high degree of conservation among different coronaviruses. Therefore inhibition of M pro has become an effective strategy for the development of broad-spectrum anti-coronaviral drugs. The inhibition of SARS-CoV-2 M pro by the anti-tumor drug carmofur has been revealed, but structural studies of carmofur in complex with M pro from other types of coronavirus have not been reported. Hence, we revealed the structure of the MERS-CoV M pro -carmofur complex, analysed the structural basis for the binding of carmofur to MERS-CoV M pro in detail, and compared the binding patterns of carmofur to M pro s of two different coronaviruses, MERS-CoV and SARS-CoV-2. Considering the importance of M pro s for coronavirus therapy, structural understanding of M pro inhibition by carmofur could contribute to the design and development of novel antiviral drugs with safe and broad-spectrum efficacy., Competing Interests: Declaration of competing interest The authors declare that no conflicts of interest exist., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Middle East Respiratory Syndrome (MERS) has become a severe zoonotic disease, posing significant public health concerns due to the lack of specific medications. This urgently demands the development of novel therapeutic molecules. Understanding MERS's genetic underpinnings and potential therapeutic targets is crucial for developing effective treatments., Methods: Two gene expression datasets (GSE81909 and GSE100504) were analyzed to identify differentially expressed genes (DEGs) using GEO2R. Furthermore, gene ontology (GO), pathway enrichment analysis, and protein-protein interaction (PPI) network were performed to understand the gene's functions. A possible drug target was identified, and an FDA-approved drug library was screened against the selected target using molecular docking and validated the findings through molecular dynamics simulation, principal component analysis, free energy landscape, and MM/GBSA calculations., Results: The study on GSE81909 and GSE100504 datasets with icMERS and MOCK samples at 24 and 48 h revealed an upregulation in 73 and 267 DEGs, respectively. In the network pharmacology, STAT1, MX1, DDX58, EIF2AK2, ISG15, IFIT1, IFIH1, OAS1, IRF9, and OASL were identified as the top 10 hub genes. STAT1 was identified as the most connected hub gene among these top 10 hub genes, which plays a crucial role in the immune response to the MERS virus. Further study on STAT1 showed that PPARG helps reduce STAT1, which could modulate the immune response. Therefore, by inhibiting PPARG, the immunological response can be successfully enhanced. The known inhibitor of PPARG, 570 (Farglitazar), was used as a control. Further, screening using Tanimoto and K-mean clustering was performed, from which three compounds were identified: 2267, 3478, and 40326. Compound 3478 showed characteristics similar to the control, indicating robust binding to PPARG. 3478 showed the highest negative binding free energy with -41.20 kcal/mol, indicating strong binding with PPARG., Conclusions: These findings suggest that 3478 promises to be a potential inhibitor of PPARG, and further experimental investigations can explore its potential as a MERS inhibitor., Competing Interests: Declaration of Competing Interest We have no conflict of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to the global pandemic of Coronavirus Disease (2019) (COVID-19), underscoring the urgency for effective antiviral drugs. Despite the development of different vaccination strategies, the search for specific antiviral compounds remains crucial. Here, we combine machine learning (ML) techniques with in vitro validation to efficiently identify potential antiviral compounds. We overcome the limited amount of SARS-CoV-2 data available for ML using various techniques, supplemented with data from diverse biomedical assays, which enables end-to-end training of a deep neural network architecture. We use its predictions to identify and prioritize compounds for in vitro testing. Two top-hit compounds, PKI-179 and MTI-31, originally identified as Pi3K-mTORC1/2 pathway inhibitors, exhibit significant antiviral activity against SARS-CoV-2 at low micromolar doses. Notably, both compounds outperform the well-known mTOR inhibitor rapamycin. Furthermore, PKI-179 and MTI-31 demonstrate broad-spectrum antiviral activity against SARS-CoV-2 variants of concern and other coronaviruses. In a physiologically relevant model, both compounds show antiviral effects in primary human airway epithelial (HAE) cultures derived from healthy donors cultured in an air-liquid interface (ALI). This study highlights the potential of ML combined with in vitro testing to expedite drug discovery, emphasizing the adaptability of AI-driven approaches across different viruses, thereby contributing to pandemic preparedness., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Several risk factors have been used to predict severity of coronavirus disease 2019 (COVID-19), real-time reverse transcriptase polymerase chain reaction (RT-PCR) cycle threshold (Ct) values have not been included. Methods: A retrospective analysis of laboratory-confirmed COVID-19 patients who were hospitalized between March 2 and September 1, 2020, in an academic hospital in Riyadh that serves as a Middle East respiratory syndrome coronavirus (MERS-CoV) referral center was conducted. Nasopharyngeal (NP) and endotracheal (ET) samples were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by RT-PCR, and viral load (VL) was determined based on the Ct values of E genes. The Ct values were distributed into four groups, with group Ct1 (≤19) indicating the highest VL and Ct4 (≥31) indicating the lowest VL. Univariate logistic regression was used to analyze age, gender, and comorbidities in relation to Ct groups for a primary endpoint of either invasive mechanical ventilation (IMV) or mortality. Significant variables were further analyzed by multivariate logistic regression. Results: The analysis included 728 patients hospitalized with COVID-19 (38% female; median age = 53 years; 41.3% diabetic; 39.4% hypertensive). Overall, 13.6% of these patients required IMV, and the in-hospital mortality rate was 15.5%. The IMV rate was higher in the Ct1 and Ct2 groups (15.2% and 15.5%, respectively) than in the Ct4 group (6.4%; p = 0.01). The mortality rate was also higher in the Ct1 and Ct2 groups (19.4% and 18.9%, respectively) than in the Ct4 group (8.9%; p = 0.02). The univariate analysis showed that lower Ct values and increasing age were associated with an increased risk of IMV (OR: 1.03; 95% CI: 1.01, 1.04; P < 0.0001) and mortality (OR: 1.04; 95% CI: 1.03, 1.06; P < 0.0001). The multivariate analysis showed that Ct1 was associated with the highest risk of mortality (OR: 2.29; 95% CI: 1.16, 5.52; P = 0.016), while Ct2 was associated with the highest risk of IMV (OR: 3.1; 95% CI: 1.47, 6.53; P = 0.003). Conclusion: The SARS-CoV-2 RT-PCR Ct values of hospitalized COVID-19 patients can be used as predictors of IMV and mortality, and this effect increases when combined with age. Clinicians could use these predictors to triage older patients for risk stratification and allocate IMV.

Objectives: Here, we prepared a liposome-based vaccine formulation containing Middle East Respiratory Syndrome Coronavirus papain-like protease (MERS-CoV-PLpro). Methods: A persistent leukopenic condition was induced in mice by injecting cyclophosphamide (CYP) three days before each dose of immunization. Mice were immunized on days 0, 14 and 21 with α-GalCer-bearing MERS-CoV PLpro-encapsulated DPPC-liposomes (α-GalCer-MERS-PLpro-liposomes or MERS-CoV PLpo-encapsulated DPPC-liposomes (MERS-PLpro-liposomes), whereas the antigen emulsified in Alum (MERS-PLpro-Alum) was taken as a control. On day 26, the blood was taken from the immunized mice to analyze IgG titer, whereas the splenocytes were used to analyze the lymphocyte proliferation and the level of cytokines. In order to assess the memory immune response, mice were given a booster dose after 150 days of the last immunization. Results: The higher levels of MERS-CoV-PLpro-specific antibody titer, IgG2a and lymphocyte proliferation were noticed in mice immunized with α-GalCer-MERS-PLpro-liposomes. Besides, the splenocytes from mice immunized with α-GalCer-MERS-PLpro-liposomes produced larger amounts of IFN-γ as compared to the splenocytes from MERS-PLpro-liposomes or MERS- PLpro-Alum immunized mice. Importantly, an efficient antigen-specific memory immune response was observed in α-GalCer-MERS-PLpro-liposomes immunized mice. Conclusions: These findings suggest that α-GalCer-MERS-PLpro-liposomes may substantiate to be a successful vaccine formulation against MERS-CoV infection, particularly in immunocompromised individuals.

Objective: To describe the clinical characteristics and outcomes of hospitalized coronavirus disease 2019 (COVID-19) patients in a middle east respiratory syndrome coronavirus (MERS-CoV) referral hospital during the peak months of the pandemic. Design: A single-center case series of hospitalized individuals with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in King Saud University Medical City (KSUMC), an academic tertiary care hospital in Riyadh, Saudi Arabia.Clinical and biochemical markers were documented. Risks for ventilatory support, intensive care unit (ICU) admission and death are presented. Results: Out of 12,688 individuals tested for SARS-CoV-2 by real time reverse transcriptase polymerase reaction (RT-PCR) from June 1 to August 31, 2020, 2,683 (21%) were positive for COVID-19. Of the latter, 605 (22%) patients required hospitalization with a median age of 55, 368 (61%) were male. The most common comorbidities were hypertension (43%) and diabetes (42%). Most patients presented with fever (66%), dyspnea (65%), cough (61%), elevated IL-6 (93.5%), D-dimer (90.1%), CRP (86.1%), and lymphopenia (41.7%). No MERS-CoV co-infection was detected. Overall, 91 patients (15%) died; risk factors associated with mortality were an age of 65 years or older OR 2.29 [95%CI 1.43–3.67], presence of two or more comorbidities OR 3.17 [95%CI 2.00–5.02], symptoms duration of seven days or less OR 3.189 [95%CI (1.64 – 6.19]) lymphopenia OR 3.388 [95%CI 2.10–5.44], high CRP OR 2.85 [95%CI 1.1–7.32], high AST OR 2.95 [95%CI 1.77–4.90], high creatinine OR 3.71 [95%CI 2.30–5.99], and high troponin-I OR 2.84 [95%CI 1.33–6.05]. Conclusion: There is a significant increase in severe cases of COVID-19. Mortality was associated with older age, shorter symptom duration, high CRP, low lymphocyte count, and end-organ damage.

Coronavirus disease 2019 (COVID-19) outbreak is proving to be an unprecedented disaster that lays its dark shadow on global health, economics and personal freedom. Severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS) epidemics provide scientific data that is useful in better understanding and resolution of COVID-19. Similarities among SARS-CoV, MERS-CoV and SARS-CoV-2 have been investigated in the light of available data. SARS-CoV, MERS-CoV and SARS-CoV-2 evolved in bats and have positive-sense RNA genomes of 27.9 kb, 30.1 kb and 29.9 kb, respectively. Molecular and serological tools used for diagnosis of SARS and MERS patients resemble COVID-19 diagnostic tools. Stability and longevity data of SARS and MERS epidemics contribute in the current pandemic precaution policies. Trials to produce vaccines for SARS-CoV and MERS-CoV failed, therefore different strategies were employed for SARS-CoV2 vaccines production and during the past period antiviral agents, Convalescent plasma and monoclonal antibodies provide potential treatments for sever patients. The mortality rate caused by the SARS-CoV and MERS-CoV reached 15% and 37%, respectively. The first declarations about mortality rate of SARS-CoV-2 was around 2–4% but now this rate differed globally and reached more than 13% in some countries. A realistic COVID-19 outbreak scenario suggest that the pandemic might last for three years with fluctuation in the number of infected cases, unless vaccination process goes faster and/or antiviral drug is discovered.

Coronaviruses are non-segmented and single stranded positive-sense RNA (+ssRNA) viruses. To date, 06 human coronaviruses (HCoVs) are reported; α-CoVs (HCoVs-NL63 and HCoVs-229E) and β-CoVs (HCoVs-OC43, HCoVs-HKU1, SARS-CoV, MERS-CoV). While, novel coronavirus (SARS-CoV-2) is the most recent member. The genome sequence of SARS-CoV-2 is 82% similar to SARS–COV-1. The compelling evidences link the progression of viral infection of SARS-CoV-2 with excessive inflammation as a result of the exaggerated immune response and elevated production of “immunocytokines” resulting in cytokine storm (CS); followed by a series of events, like acute organ damage, acute respiratory distress syndrome (ARDS) as well as death. Hence attempts to reduce cytokine storm are now being considered as a new paradigm shift in the clinical management of SARS-CoV-2. Tocilizumab (IL-6 blocker), Baricitinib (JAKs and AAK1 inhibitor), TNFα inhibitors (Infliximab, Adalimumab, Certolizumab) are currently being evaluated for possible block of the CS. Hence, rationalizing anti-inflammatory therapeutics would be the most judicious approach for significant reduction in COVID-19 mortality. In order to elucidate optimized and rationaled use of different therapeutics in COVID-19, we collated latest available information from emerging scientific evidences, integrated previous attempts as well as clinical successes, and various adopted approaches to mitigate past outbreaks with of SARS-CoV and MERS CoV.

Background: The MERS-CoV was identified for the first time from Jeddah, Saudi Arabia in 2012 from a hospitalized patient. This virus has now been spread to 27 countries with a total of 858 deaths and 2494 confirmed cases and has become a serious concern for the human population. Camels are well known for the transmission of the virus to the human population. Methods: In this report, we have discussed the designing, prediction, and evaluation of potential siRNAs against the orf1ab gene of MERS-CoV. The online software was used to predict and design the siRNAs and finally, total twenty-one siRNA were filtered out from four hundred and sixty-two sIRNAs as per their scoring and specificity criteria. We have used only ten siRNAs to evaluate their cytotoxicity and efficacy by reverse transfection approach in HEK-293-T cell lines. Results: Based on the results and data generated; no cytotoxicity was observed for any siRNAs at various concentrations in HEK-293-T cells. The ct value of real-time PCR showed the inhibition of viral replication in siRNA-1, 2, 4, 6, and 9. The data generated provided the preliminary information and encouraged us to evaluate the remaining siRNAs separately as well as in combination to analyses the replication of MERS-CoV inhibition in other cell lines. Conclusion: Based on the results obtained; it is concluded that the prediction of siRNAs using online software resulted in the filtration of potential siRNAs with high accuracy and strength. This technology can be used to design and develop antiviral therapy not only for MERS-CoV but also against other viruses.

Resumen: SARS-CoV-2 es el tercer coronavirus que emerge en las últimas dos décadas y produce la enfermedad denominada COVID-19 (enfermedad infecciosa por coronavirus 2019). Ha demostrado ser fácilmente transmisible entre humanos con una rápida diseminación mundial y declarada como pandemia el 11 de marzo 2020. A la fecha ha causado millones de casos y muertes, disrupción de servicios sanitarios y severas consecuencias sociales, económicas y políticas en todos los países. Los estudios filogenéticos lo relacionan con SARS-CoV presentes en murciélagos. Comparte características de patogenicidad con sus parientes más cercanos, SARS-CoV y MERS-CoV. 15 a 20% de los afectados presentan cuadros graves. A la fecha no se cuenta con antivirales efectivos ni vacunas. Para un adecuado control se hace imprescindible dilucidar aspectos epidemiológicos, moleculares y de patogenicidad. En esta revisión se presenta información básica sobre epidemiología, origen, estructura y patogenia de SARS-CoV-2. Summary: SARS-CoV-2 is the third coronavirus emerging in the last two decades producing a disease denominated COVID-19 (infectious disease by coronavirus 2019). It has demostrated to be easily transmisible between humans with a fast world wide dissemination and declared a pandemia in March 11, 2020. Up to date it has caused millions of cases, deaths, disruptions in medical services and severe social, political and economic consecuences, all around the globe. Phylogenetic studies relate it to SARS-CoV present in bats. It shares pathogenic characteristics with its close relatives, SARS-CoV and MERS-CoV. 15 to 20% of the patients develop a severe clinical course. Up to date there are no effective antiviral drugs or vaccines. For an adecuate control it is essential to learn about epidemiological, pathogenic and molecular aspects. In this review some basic information about epidemiology, origin source, structure and pathogenicity of SARS-CoV-2 is presented.

Viruses often encode proteins that mimic host proteins in order to facilitate infection. Little work has been done to understand the potential mimicry of the SARS-CoV-2, SARS-CoV, and MERS-CoV spike proteins, particularly the receptor-binding motifs, which could be important in determining tropism and druggability of the virus. Peptide and epitope motifs have been detected on coronavirus spike proteins using sequence homology approaches; however, comparing the three-dimensional shape of the protein has been shown as more informative in predicting mimicry than sequence-based comparisons. Here, we use structural bioinformatics software to characterize potential mimicry of the three coronavirus spike protein receptor-binding motifs. We utilize sequence-independent alignment tools to compare structurally known protein models with the receptor-binding motifs and verify potential mimicked interactions with protein docking simulations. Both human and non-human proteins were returned for all three receptor-binding motifs. For example, all three were similar to several proteins containing EGF-like domains: some of which are endogenous to humans, such as thrombomodulin, and others exogenous, such as Plasmodium falciparum MSP-1. Similarity to human proteins may reveal which pathways the spike protein is co-opting, while analogous non-human proteins may indicate shared host interaction partners and overlapping antibody cross-reactivity. These findings can help guide experimental efforts to further understand potential interactions between human and coronavirus proteins.

The papain-like protease (PLpro) is vital for the replication of coronaviruses (CoVs), as well as for escaping innate-immune responses of the host. Hence, it has emerged as an attractive antiviral drug-target. In this study, computational approaches were employed, mainly the structure-based virtual screening coupled with all-atom molecular dynamics (MD) simulations to computationally identify specific inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PLpro, which can be further developed as potential pan-PLpro based broad-spectrum antiviral drugs. The sequence, structure, and functional conserveness of most deadly human CoVs PLpro were explored, and it was revealed that functionally important catalytic triad residues are well conserved among SARS-CoV, SARS-CoV-2, and middle east respiratory syndrome coronavirus (MERS-CoV). The subsequent screening of a focused protease inhibitors database composed of ∼7,000 compounds resulted in the identification of three candidate compounds, ADM_13083841, LMG_15521745, and SYN_15517940. These three compounds established conserved interactions which were further explored through MD simulations, free energy calculations, and residual energy contribution estimated by MM-PB(GB)SA method. All these compounds showed stable conformation and interacted well with the active residues of SARS-CoV-2 PLpro, and showed consistent interaction profile with SARS-CoV PLpro and MERS-CoV PLpro as well. Conclusively, the reported SARS-CoV-2 PLpro specific compounds could serve as seeds for developing potent pan-PLpro based broad-spectrum antiviral drugs against deadly human coronaviruses. Moreover, the presented information related to binding site residual energy contribution could lead to further optimization of these compounds.

Background: Middle East respiratory syndrome coronavirus (MERS-CoV) has continued to cause sporadic outbreaks of severe respiratory tract infection over the last 8 years. Methods: Complete genome sequencing using next-generation sequencing was performed for MERS-CoV isolates from cases that occurred in Riyadh between 2015 and 2019. Phylogenetic analysis and molecular mutational analysis were carried out to investigate disease severity. Results: A total of eight MERS-CoV isolates were subjected to complete genome sequencing. Phylogenetic analysis resulted in the assembly of 7/8 sequences within lineage 3 and one sequence within lineage 4 showing complex genomic recombination. The isolates contained a variety of unique amino acid substitutions in ORF1ab (41), the N protein (10), the S protein (9) and ORF4b (5). Conclusion: Our study shows that MERS-CoV is evolving. The emergence of new variants carries the potential for increased virulence and could impose a challenge to the global health system. We recommend the sequencing every new MERS-CoV isolate to observe the changes in the virus and relate them to clinical outcomes.

Introduction: MERS is caused by a viral infection, which was first identified in KSA, 2012. MERS-CoV infection consequences with either hospitalization or death. Methods: All positive MERS-CoV cases that diagnosed in and reported to a referral hospital in Najran, KSA from March/2014 to December/2018 were revised retrospectively. We identified patients from infection control department and medical records. Demographic, clinical, and outcome data were collected. Results: Of the 54 positive MERS-CoV cases, 3 cases were excluded because no available data. Therefore, the final number of the included cases in the study was 51 cases (94.4). Most of the patients were Saudi 36 (70.6%), and majority of cases were reported in the winter 18 (35.3) season. Fever 47 (92.2%), cough 44 (86.3%), and shortness of breath 37 (72.5%) were reported as most common symptoms. Most patients had diabetes mellitus and hypertension. Overall mortality rate was 37.3%, and interestingly the mortality rate dropped sharply over 5 years. In logistic regression analysis, Season and Chronic Kidney disease patients were the only two variables statistically significantly associated with death. The odds of death the patients infected by MERS-CoV during Autumn and Winter season were 4.09 times higher than those patients who infected during Spring and Summer season (OR = 4.09, CI 1.18-14.15, P < 0.026). Compared with MERS-CoV patients who had Non-Chronic kidney diseases, the odds of death the MERS-CoV patients who had chronic kidney diseases were 18.08 times higher (OR = 18.08, CI -2.01-162.99, P < 0.01). Conclusion: The case fatality rate of MERS-CoV infection was high. Further studies with large sample sizes are needed to explore the reasons behind the decrease in the mortality rate over the time period.

Coronaviruses (CoVs), a family of enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, unusually large RNA genome, and unique replication capability. CoVs are known to cause various potentially lethal human respiratory infectious diseases, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the very recent coronavirus disease 2019 (COVID-19) outbreak. Unfortunately, neither drug nor vaccine has yet been approved to date to prevent and treat these diseases caused by CoVs. Therefore, effective prevention and treatment medications against human coronavirus are in urgent need. In the past decades, many natural compounds have been reported to possess multiple biological activities, including antiviral properties. In this article, we provided a comprehensive review on the natural compounds that interfere with the life cycles of SARS and MERS, and discussed their potential use for the treatment of COVID-19.

Coronaviruses (CoVs) are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has caused major public health crises. There have been more than 4,400,000 reported cases of COVID-2019 and more than 300,000 reported deaths to date (16/05/2020). SARS-CoV, MERS-CoV and SARS-CoV-2 have attracted widespread global attention due to their high infectivity and pathogenicity. To date, there is no specific treatment proven effective against these viral infectious diseases. Vaccination is considered one of the most effective strategies to prevent viral infections. Therefore, the development of effective vaccines against highly pathogenic coronaviruses is essential. In this review, we will briefly describe coronavirus vaccine design targets, summarize recent advances in the development of coronavirus vaccines, and highlight current adjuvants for improving the efficacy of coronavirus vaccines.

Nearly four months have passed since the emergence of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which caused the rapidly spreading Coronavirus Disease 2019 (COVID-19) pandemic. To date, there have been more than 2.3 million confirmed cases and more than 160,000 deaths globally caused by COVID-19. Chinese health authorities, where the virus emerged, have taken prompt strict public health measures to control and prevent the spread of the outbreak. In Saudi Arabia, unprecedented precautionary strict measures were applied to prevent virus entry to the country or to mitigate its impact when it arrives. Here, we review the response of Saudi Arabia to COVID-19 pandemic and how did the experience learned from the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic since 2012 has helped the country to be better prepared for the current COVID-19 pandemic. We also discuss the country readiness, improvement in research and development, and the unprecedented rapid precautionary measures that have been taken by the Saudi government thus far.

The Middle East respiratory syndrome (MERS) is a lethal zoonosis caused by MERS coronavirus (MERS-CoV) and poses a significant threat to public health worldwide. Therefore, a rapid, sensitive, and specific serologic test for detecting anti-MERS-CoV antibodies in both humans and animals is urgently needed for the successful management of this illness. Here, we evaluated various novel luciferase immunosorbent assays (LISA) based on nucleocapsid protein (NP) as well as fragments derived from spike protein (S) including subunit 1 (S1), N terminal domain (NTD), receptor-binding domain (RBD) and subunit 2 (S2) of S for the detection of MERS-CoV-specific IgG. Fusion proteins, including nanoluciferase (NLuc) and various fragments derived from the NP or S protein of MERS-CoV, were expressed in human embryonic kidney 293 T cells. LISAs that detected anti-MERS-CoV IgG were further developed using cell lysates expressing various fusion proteins. Panels of human or animal samples infected with MERS-CoV were used to analyze the sensitivity and specificity of various LISAs in reference to a MERS-CoV RT-PCR, commercial S1-based ELISA, and pseudovirus particle neutralization test (ppNT). Our results showed that the S1-, RBD-, and NP-LISAs were more sensitive than the NTD- and S2-LISAs for the detection of anti-MERS-CoV IgG. Furthermore, the S1-, RBD-, and NP-LISAs were more sensitive (by at least 16-fold) than the commercially available S1-ELISA. Moreover, the S1-, RBD-, and NP-LISA specifically recognized anti-MERS-CoV IgG and did not cross-react with samples derived from other human CoV (OC43, 229E, HKU1, NL63)-infected patients. More importantly, these LISAs proved their applicability and reliability for detecting anti-MERS-CoV IgG in samples from camels, monkeys, and mice, among which the RBD-LISA exhibited excellent performance. The results of this study suggest that the novel MERS-CoV RBD- and S1- LISAs are highly effective platforms for the rapid and sensitive detection of anti-MERS-CoV IgG in human and animal samples. These assays have the potential to be used as serologic tests for the management and control of MERS-CoV infection.

Background: Of the three lethal coronaviruses, in addition to the ongoing pandemic-causing SARS-CoV 2, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) remains in circulation. Information on MERS-CoV has relied on small sample of patients. We updated the epidemiology, laboratory and clinical characteristics, and survival patterns of MERS-CoV retrospectively with the largest sample of followed patients. Methods: We conducted a retrospective review of line-listed records of non-random, continuously admitted patients who were suspected (6,873) or confirmed with MERS-CoV (501) admitted to one of the four MERS-CoV referral hospitals in Saudi Arabia, 2014-2019. Findings: Of the 6,873 MERS-CoV suspected persons, the majority were male (56%) and Saudi nationals (83%) and 95% had no known history that increased their risk of exposure to MERS-CoV patients or vectors (95%). More confirmed cases reported history that increased their risk of MERS-CoV infection (41%). Among the suspected, MERS-CoV confirmation (7.4% overall) was independently associated with being male, known transmission link to MERS-CoV patients or vectors, fever, symptoms for 7 days, admission through intensive care unit, and diabetes. Among persons with confirmed MERS-CoV, single symptoms were reported by 20%, 3-symptom combinations (fever, cough and dyspnea) reported by 21% and 2-symptom combinations (fever, cough) reported by 16%. Of the two-thirds (62%) of MERS-CoV confirmed patients who presented with co-morbidity, 32% had 2-''comorbidities (diabetes, hypertension). More than half of the MERS-CoV patents showed abnormal chest X-ray, elevated aspartate aminotransferase, and creatinine kinase. About a quarter of MERS-CoV patients had positive cultures on blood, urine, or respiratory secretions. During an average hospital stay of 18 days (range 11 to 30), 64% developed complications involving liver, lungs, or kidneys. Ventilation requirement (29% of MERS-CoV cases) was independently associated with abnormal chest X-ray, viremia (Ct value

To generate baseline information to help better understand the antibody kinetics and nasal shedding dynamics of MERS-CoV in camels in Jordan, a longitudinal surveillance study was conducted in two phases; phase 1 was between December, 2018 and January, 2019 and phase 2 between August and December 2020. In each phase, two camel herds were studied. These herds were located in Al-azraq and in Al-ramtha area and were named Al-azraq and Al-ramtha herds, respectively. The same camel herd of Al-zarqa area was sampled in both phases while two different camel herds, one in each phase, were sampled in Al-ramtha area. Blood and nasal swabs were collected from same selected animals in all visits to each herd in both phases. Additionally, nasal swabs and retropharyngeal lymph node tissue samples were collected from sixty-one camels slaughtered at Al-ramtha abattoir during phase 2 to enhance virus isolation opportunities and phylogenetic analysis. All sampled animals from Al-azraq camel herd were either borderline or seropositive on spike 1 based ELISA assay and negative on quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in both phases. In Al-ramtha camel herds, an unsteady pattern prevailed in animals’ seropositivity in both phases and viral RNA was detected in all animals in the end of phase 1 and in one animal during phase 2. For the seroconversion, anti-MERS-CoV spike 1 antibodies were detected in two animals in phase 1 in the first collection only. While, in phase 2, intermittent seroconversion pattern was observed in several samples over time of collections that ended with all animals became seropositive in the last collection (after nineteen days from viral RNA detection). In addition, viral RNA was detected in nasal swabs of 3 slaughtered camels. Phylogenetic analysis of a partial fragment of spike 1 gene sequences of all MERS-CoV isolates clustered together with clade B of MERS-CoV. This cluster contains all MERS-CoV sequences obtained either from camels or human sources in the Arabian Peninsula indicating the continuous circulation of this clade also in Jordan.

Convalescent plasma therapy (CPT) is one of the well-known therapeutic protocols for treating infectious diseases that do not have special treatment or vaccine. Several documents confirm the clinical efficacy of this therapy for treating bacterial and viral infections. A comprehensive systematic search was conducted by August 2020 using global databases including PubMed, Scopus, Embase, Cochrane library, Google scholar, medRxiv and bioRxiv. The Joanna Briggs Institute critical appraisal checklist was used to evaluate the included studies. Using the Comprehensive Meta-Analysis software version 2.2 (Biostat, Englewood, NJ, USA), the pooled data analysis process was performed. A total of 15 eligible articles were enrolled in the current quantitative synthesis. The statistical analysis showed that clinical improvement in the group of patients who had received convalescent plasma was significantly increased compared with the control group (OR: 2.23; 1.12-4.45 with 95% CIs; p value: 0.022; Q-value: 6.11; I2: 83.64; Eggers p value: 0.064; Beggs p value: 0.093). Furthermore, the rate of hospital discharge had increased in patients receiving CPT (OR: 2.92; 1.48-5.77 with 95% CIs; p value: 0.002; Q-Value: 4.32; I2: 53.80; Eggers p value: 0.32; Beggs p value: 0.50). Because there is currently no fully effective antiviral drug against the virus and it will take time to confirm the effectiveness of new drugs, CPT can be used as an alternative treatment strategy to improve the severe clinical manifestations of COVID-19.

Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the causative etiology of ‘Corona Virus Disease-2019’ (COVID-19); formerly referred as ‘novel-Coronavirus-2019’. It was originated in Wuhan city, Hubei province, China in early December 2019. The World Health Organization (WHO) declared it as ‘Public Health Emergency of International Concern’ due to their rapid transmission and causing public and health-care-related casualties worldwide. This review provides an updated overview of COVID-19 (SARS-CoV-2), in comparison with the etiologies of the same group viz. SARS and MERS and also its future perspectives for planning appropriate strategies for prevention, control and treatment modalities to avert similar catastrophe in near future.

Coronaviruses M proteins are well-represented in the major protein component of the viral envelope. During the viral assembly, they play an important role by association with all other viral structural proteins. Despite their crucial functions, very little information regarding the structures and functions of M proteins is available. Here we utilize bioinformatic tools from available sequences and 3D structures of SARS-CoV, SARS-CoV2, and MERS-CoV M proteins in order to predict potential B-cell epitopes and assessing antibody binding affinity. Such study aims to aid finding more effective vaccines and recognize neutralizing antibodies. we found some rather exciting differences between SARS-COV-2, SARS-Cov and MERS-CoV M proteins. Two SARS-CoV-2 peptides with significant antigen presentation scores for human cell surface proteins have been identified. The results reveal that N-terminal domains of M proteins of SARS-CoV and SARS-CoV2 are translocated (outside) whereas it is inside (cytoplasmic side) in MERS-CoV.

Summary: Integrated, up-to-date data about SARS-CoV-2 and COVID-19 is crucial for the ongoing response to the COVID-19 pandemic by the biomedical research community. While rich biological knowledge exists for SARS-CoV-2 and related viruses (SARS-CoV, MERS-CoV), integrating this knowledge is difficult and time-consuming, since much of it is in siloed databases or in textual format. Furthermore, the data required by the research community vary drastically for different tasks; the optimal data for a machine learning task, for example, is much different from the data used to populate a browsable user interface for clinicians. To address these challenges, we created KG-COVID-19, a flexible framework that ingests and integrates heterogeneous biomedical data to produce knowledge graphs (KGs), and applied it to create a KG for COVID-19 response. This KG framework also can be applied to other problems in which siloed biomedical data must be quickly integrated for different research applications, including future pandemics. The Bigger Picture: An effective response to the COVID-19 pandemic relies on integration of many different types of data available about SARS-CoV-2 and related viruses. KG-COVID-19 is a framework for producing knowledge graphs that can be customized for downstream applications including machine learning tasks, hypothesis-based querying, and browsable user interface to enable researchers to explore COVID-19 data and discover relationships.

The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. The objective of the study was to describe the epidemiology, risk factors, clinical characteristics, and outcome of MERS-CoV in Qatar. A total of 28 cases of MERS-CoV were identified, corresponding to an incidence of 1.7 per 1,000,000 population. Most patients had a history of contact with camels 15, travel to Kingdom of Saudi Arabia 7 or known contact with individuals with confirmed MERS-CoV infection 7. Majority of patients had acute kidney injury (AKI) 17 and 9 needed renal replacement therapy. All patients were hospitalized, 14 required critical care support. Overall, total of 10 died. The immediate cause of death was multiorgan failure with acute respiratory syndrome (ARDS) 9. MERS-CoV is a rare infection in the State of Qatar. There was no hospital outbreaks or healthcare worker reported infection. The infection causes severe respiratory failure and acute renal failure. Patients with AKI and on ventilator support carry higher risk of mortality.

The severe acute respiratory syndrome cornavirus (SARS-CoV-2) is a new human coronavirus candidate recently detected in China that is now reported in people on inhabited continents. The virus shares a high level of identity with some bat coronaviruses and is recognised as a potentially zoonotic virus. We are utilizing the One Health concept to understand the emergence of the virus, as well as to point to some possible control strategies that might reduce the spread of the virus across the globe; thus, containment of such virus would be possible.

Severe Middle East respiratory syndrome (MERS) is characterized by massive infiltration of immune cells in lungs. MERS-coronavirus (MERS-CoV) replicates in vitro in human macrophages, inducing high pro-inflammatory responses. In contrast, camelids, the main reservoir for MERS-CoV, are asymptomatic carriers. Although limited infiltration of leukocytes has been observed in the lower respiratory tract of camelids, their role during infection remains unknown. Here we studied whether llama alveolar macrophages (LAMs) are susceptible to MERS-CoV infection and can elicit pro-inflammatory responses. MERS-CoV did not replicate in LAMs; however, they effectively capture and degrade viral particles. Moreover, transcriptomic analyses showed that LAMs do not induce pro-inflammatory cytokines upon MERS-CoV sensing., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause frequent hospital outbreaks in Saudi Arabia, with emergency departments as the initial site of the spread of this virus. Methods: The risk of transmission of MERS-CoV infection to healthcare workers (HCWs) was assessed in an outbreak in Riyadh. All HCWs with unprotected exposure to confirmed cases were tested after 24 h of exposure. Two negative results for MERS-CoV obtained 3 days apart and being free of any suggestive signs and symptoms were used to end the isolation of the HCWs and allow their return to duty. Results: Overall 17 out of 879 HCWS with different levels of exposure tested positive for MERS-CoV. Of the 15 positive HCWS with adequate follow-up, 40% (6/15 HCWs) tested positive on the first sampling and 53% (8/15) tested positive on the second sampling. The time to negative results among the 15 positive HCWs ranged between 4 and 47 days (average 14.5 days) and the infected HCWs needed on average two samples for clearance. All positive HCWs were either asymptomatic or had mild disease. Conclusions: The data obtained in this study support the widespread testing of all close contacts of MERS-CoV cases, regardless of the significance of the contact or presence or absence of symptoms. In addition, urgent careful review of guidance regarding the return of asymptomatic MERS-CoV-positive HCWs under investigation to active duty is needed.

Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV), a member of the Coronaviridae family, is the causative pathogen for MERS that is characterized by high fever, pneumonia, acute respiratory distress syndrome (ARDS), as well as extrapulmonary manifestations. Currently, there are no approved treatment regimens or vaccines for MERS. Here, we generated recombinant nonvirulent Newcastle disease virus (NDV) LaSota strain expressing MERS-CoV S protein (designated as rLa-MERS-S), and evaluated its immunogenicity in mice and Bactrian camels. The results revealed that rLa-MERS-S showed similar growth properties to those of LaSota in embryonated chicken eggs, while animal immunization studies showed that rLa-MERS-S induced MERS-CoV neutralizing antibodies in mice and camels. Our findings suggest that recombinant rLa-MERS-S may be a potential MERS-CoV veterinary vaccine candidate for camels and other animals affected by MERS.

Background: Although the literature indicates that patient delays in seeking medical support for Middle East respiratory syndrome coronavirus (MERS-CoV) infections are associated with poor clinical outcomes, delays in the diagnosis itself remain poorly understood in these patients. This study aimed to determine the median time interval from symptom onset to a confirmed diagnosis and to identify the potential predictors of this interval in Saudi Arabian MERS patients. Methods: This was a retrospective study of patients with confirmed MERS who were publicly reported by the World Health Organization (WHO). Results: Five hundred and thirty-seven symptomatic cases of MERS-CoV infection were included. The median time interval between symptom onset and confirmation of the MERS diagnosis was 4 days (interquartile range 2–7 days), ranging from 0 to 36 days. According to the negative binomial model, the unadjusted rate ratio (RR) of delays in the diagnosis was significantly higher in older patients (>65 years) (RR 1.42), non-healthcare workers (RR 1.74), patients with severe illness (RR 1.22), those with an unknown source of infection (RR 1.84), and those who had been in close contact with camels (RR 1.74). After accounting for confounders, the adjusted rate ratio (aRR) of delays in the diagnosis was independently associated with unknown source of infection (aRR 1.68) and close contact with camels (aRR 1.58). Conclusions: The time interval from symptom onset to diagnosis was greater in older patients, non-healthcare workers, patients with severe illness, patients with an unknown source of infection, and patients who had been in close contact with camels. The findings warrant educational interventions to raise general public awareness of the importance of early symptom notification.

Coronaviruses pose a permanent risk of outbreaks, with three highly pathogenic species and strains (SARS-CoV, MERS-CoV, SARS-CoV-2) having emerged in the last twenty years. Limited antiviral therapies are currently available and their efficacy in randomized clinical trials enrolling SARS-CoV-2 patients has not been consistent, highlighting the need for more potent treatments. We previously showed that cobicistat, a clinically approved inhibitor of Cytochrome P450-3A (CYP3A), has direct antiviral activity against early circulating SARS-CoV-2 strains in vitro and in Syrian hamsters. Cobicistat is a derivative of ritonavir, which is co-administered as pharmacoenhancer with the SARS-CoV-2 protease inhibitor nirmatrelvir, to inhibit its metabolization by CPY3A and preserve its antiviral efficacy. Here, we used automated image analysis for a screening and parallel comparison of the anti-coronavirus effects of cobicistat and ritonavir. Our data show that both drugs display antiviral activity at low micromolar concentrations against multiple SARS-CoV-2 variants in vitro, including epidemiologically relevant Omicron subvariants. Despite their close structural similarity, we found that cobicistat is more potent than ritonavir, as shown by significantly lower EC50 values in monotherapy and higher levels of viral suppression when used in combination with nirmatrelvir. Finally, we show that the antiviral activity of both cobicistat and ritonavir is maintained against other human coronaviruses, including HCoV-229E and the highly pathogenic MERS-CoV. Overall, our results demonstrate that cobicistat has more potent anti-coronavirus activity than ritonavir and suggest that dose adjustments could pave the way to the use of both drugs as broad-spectrum antivirals against highly pathogenic human coronaviruses., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Iart Luca Shytaj is inventor of a patent application covering the use of cobicistat for treatment of coronavirus infection., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The COVID-19 pandemic caused by SARS-CoV-2, lead to mild to severe respiratory illness and resulted in 6.9 million deaths worldwide. Although vaccines are effective in preventing COVID-19, they may not be sufficient to protect immunocompromised individuals from this respiratory illness. Moreover, novel emerging variants of SARS-CoV-2 pose a risk of new COVID-19 waves. Therefore, identification of effective antivirals is critical in controlling SARS and other coronaviruses, such as MERS-CoV. We show that Fangchinoline (Fcn), a bisbenzylisoquinoline alkaloid, inhibits replication of SARS-CoV, SARS-CoV-2, and MERS-CoV in a range of in vitro assays, by blocking entry. Therapeutic use of Fcn inhibited viral loads in the lungs, and suppressed associated airway inflammation in hACE2. Tg mice and Syrian hamster infected with SARS-CoV-2. Combination of Fcn with remdesivir (RDV) or an anti-leprosy drug, Clofazimine, exhibited synergistic antiviral activity. Compared to Fcn, its synthetic derivative, MK-04-003, more effectively inhibited SARS-CoV-2 and its variants B.1.617.2 and BA.5 in mice. Taken together these data demonstrate that Fcn is a pan beta coronavirus inhibitor, which possibly can be used to combat novel emerging coronavirus diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The appearance of novel pathogens of humans with epidemic potential and high mortality rates have threatened global health security for centuries. Over the past few decades new zoonotic infectious diseases of humans caused by pathogens arising from animal reservoirs have included West Nile virus, Yellow fever virus, Ebola virus, Nipah virus, Lassa Fever virus, Hanta virus, Dengue fever virus, Rift Valley fever virus, Crimean-Congo haemorrhagic fever virus, severe acute respiratory syndrome coronavirus, highly pathogenic avian influenza viruses, Middle East Respiratory Syndrome Coronavirus, and Zika virus. The recent Ebola Virus Disease epidemic in West Africa and the ongoing Zika Virus outbreak in South America highlight the urgent need for local, regional and international public health systems to be be more coordinated and better prepared. The One Health concept focuses on the relationship and interconnectedness between Humans, Animals and the Environment, and recognizes that the health and wellbeing of humans is intimately connected to the health of animals and their environment (and vice versa). Critical to the establishment of a One Health platform is the creation of a multidisciplinary team with a range of expertise including public health officers, physicians, veterinarians, animal husbandry specialists, agriculturalists, ecologists, vector biologists, viral phylogeneticists, and researchers to co-operate, collaborate to learn more about zoonotic spread between animals, humans and the environment and to monitor, respond to and prevent major outbreaks. We discuss the unique opportunities for Middle Eastern and African stakeholders to take leadership in building equitable and effective partnerships with all stakeholders involved in human and health systems to take forward a ‘One Health’ approach to control such zoonotic pathogens with epidemic potential.

A high percentage (up to 90%) of dromedary camels in the Middle East as well as eastern and central Africa have antibodies to Middle East respiratory syndrome coronavirus (MERS-CoV). Here we report comparably high positivity of MERS-CoV antibodies in dromedary camels from northern Mali. This extends the range of MERS-CoV further west in Africa than reported to date and cautions that MERS-CoV should be considered in cases of severe respiratory disease in the region.

Background: Development an effective vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) is urgent and limited information is available on vaccination in nonhuman primate (NHP) model. We herein report of evaluating a recombinant receptor-binding domain (rRBD) protein vaccine in a rhesus macaque model. Methods: Nine monkeys were randomly assigned to high-dose, low-dose and mock groups,which were immunized with different doses of rRBD plus alum adjuvant or adjuvant alone at different time points (0, 8, 25 weeks). Immunological analysis was conducted after each immunisation. Monkeys were challenged with MERS-CoV at 14 days after the final immunisation followed by observation for clinical signs and chest X-rays. Nasal, oropharyngeal and rectal swabs were also collected for analyses. Monkeys were euthanized 3 days after challenge and multiple specimens from tissues were collected for pathological, virological and immunological tests. Conclusion: Robust and sustained immunological responses (including neutralisation antibody) were elicited by the rRBD vaccination. Besides, rRBD vaccination alleviated pneumonia with evidence of reduced tissue impairment and clinical manifestation in monkeys. Furthermore, the rRBD vaccine decreased viral load of lung, trachea and oropharyngeal swabs of monkeys. These data in NHP paves a way for further development of an effective human vaccine against MERS-CoV infection.