UNASSIGNED: Middle East respiratory syndrome (MERS) is a viral illness caused by the MERS-Coronavirus (MERS-CoV) that was first identified in Saudi Arabia in 2012. Saudi Arabia has reported most global MERS-CoV cases and deaths, with periodic outbreaks in other countries.
UNASSIGNED: This review aims to provide a comprehensive overview of the 2023 MERS-CoV outbreak in Saudi Arabia, including its epidemiology, public health response, impact, and lessons learned.
UNASSIGNED: This study utilized a narrative review approach, drawing on published literature and data from sources such as the WHO and the Centers for Disease Control and Prevention.
UNASSIGNED: The 2023 outbreak was centered in the Riyadh region, with 312 confirmed cases and 97 deaths reported. MERS-CoV primarily spreads from dromedary camels to humans, with human-to-human transmission, especially in healthcare settings. The outbreak exhibited seasonal and spatial trends, with most cases during camel calving season and in rural areas with high camel populations. The Saudi Ministry of Health implemented a multi-faceted response, including enhancing surveillance, improving infection prevention, providing clinical support, and conducting risk communication. Over time, the response showed a decline in the number of cases and deaths, indicating its effectiveness.
UNASSIGNED: The outbreak has significant public health, economic, and social impacts, underscoring the ongoing threat of emerging zoonotic diseases. Key lessons include early case detection, efficient infection control, vaccine and treatment development, public engagement, and strengthening of regional and global collaboration to mitigate future outbreaks and safeguard public health.

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 (Mpro) plays a crucial role in the MERS-CoV life cycle, and Mpro exhibited a high degree of conservation among different coronaviruses. Therefore inhibition of Mpro has become an effective strategy for the development of broad-spectrum anti-coronaviral drugs. The inhibition of SARS-CoV-2 Mpro by the anti-tumor drug carmofur has been revealed, but structural studies of carmofur in complex with Mpro from other types of coronavirus have not been reported. Hence, we revealed the structure of the MERS-CoV Mpro-carmofur complex, analysed the structural basis for the binding of carmofur to MERS-CoV Mpro in detail, and compared the binding patterns of carmofur to Mpros of two different coronaviruses, MERS-CoV and SARS-CoV-2. Considering the importance of Mpros for coronavirus therapy, structural understanding of Mpro inhibition by carmofur could contribute to the design and development of novel antiviral drugs with safe and broad-spectrum efficacy.

UNASSIGNED: Highly pathogenic coronaviruses (CoVs), such as severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and the most recent SARS-CoV-2 responsible for the COVID-19 pandemic, pose significant threats to human populations over the past two decades. These CoVs have caused a broad spectrum of clinical manifestations ranging from asymptomatic to severe distress syndromes (ARDS), resulting in high morbidity and mortality.
UNASSIGNED: The accelerated advancements in antiviral drug discovery, spurred by the COVID-19 pandemic, have shed new light on the imperative to develop treatments effective against a broad spectrum of CoVs. This perspective discusses strategies and lessons learnt in targeting viral non-structural proteins, structural proteins, drug repurposing, and combinational approaches for the development of antivirals against CoVs.
UNASSIGNED: Drawing lessons from the pandemic, it becomes evident that the absence of efficient broad-spectrum antiviral drugs increases the vulnerability of public health systems to the potential onslaught by highly pathogenic CoVs. The rapid and sustained spread of novel CoVs can have devastating consequences without effective and specifically targeted treatments. Prioritizing the effective development of broad-spectrum antivirals is imperative for bolstering the resilience of public health systems and mitigating the potential impact of future highly pathogenic CoVs.

Background Coronaviruses (CoVs) pose significant health risks to humans, with recent outbreaks like severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscoring their zoonotic potential. Dromedary camels (Camelus dromedarius) have been implicated as intermediate hosts for MERS-CoV, prompting heightened surveillance efforts. This study aims to identify non-MERS-CoV CoVs in imported camels at the Jeddah seaport, Saudi Arabia, using molecular techniques. Methods Camel nasal swabs (n = 337) were collected from imported dromedary camels arriving at the Jeddah Islamic seaport from Sudan and Djibouti. Samples were tested for CoVs using real-time real-time reverse transcription polymerase chain reaction (RT-PCR) targeting the RNA-dependent RNA polymerase gene. Positive samples were confirmed by conventional RT-PCR and Sanger sequencing. Selected samples underwent RNA sequencing to identify viral genomes. The study underscores the importance of molecular surveillance in camels to mitigate zoonotic risks. Results Out of 337 camel samples tested, 28 (8.30%) were positive for CoVs, predominantly from camels imported from Djibouti, compared to Sudan (13.39% vs. 5.78%). Sequence analysis confirmed the presence of non-MERS CoVs, including camel alpha-coronavirus and human CoV-229E-related strains. These findings highlight potential viral diversity and transmission risks in imported camel populations. Conclusion This study identifies diverse CoVs circulating in imported dromedary camels at the Jeddah Islamic seaport, Saudi Arabia, underscoring their potential role in zoonotic transmission. Enhanced surveillance and collaborative efforts are essential to mitigate public health risks associated with novel coronavirus strains from camel populations.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC), which first emerged in 2012, persist and continue to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After the extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction in viral burdens by >6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).

Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in 2012 and causes human infections in endemic regions. Vaccines and therapeutics in development against MERS-CoV focus on the spike (S) glycoprotein to prevent viral entry into target cells. These efforts are limited by a poor understanding of antibody responses elicited by infection. Here, we analyze S-directed antibody responses in plasma collected from MERS-CoV-infected individuals. We observe that binding and neutralizing antibodies peak 1-6 weeks after symptom onset/hospitalization, persist for at least 6 months, and neutralize human and camel MERS-CoV strains. We show that the MERS-CoV S1 subunit is immunodominant and that antibodies targeting S1, particularly the receptor-binding domain (RBD), account for most plasma neutralizing activity. Antigenic site mapping reveals that plasma antibodies frequently target RBD epitopes, whereas targeting of S2 subunit epitopes is rare. Our data reveal the humoral immune responses elicited by MERS-CoV infection, which will guide vaccine and therapeutic design.

UNASSIGNED: An important respiratory pathogen that has led to multiple hospital outbreaks both inside and outside of the Arabian Peninsula is the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Given the elevated case fatality rate, there exists a pressing requirement for efficacious therapeutic agents.
UNASSIGNED: This is an updated review of the developments in MERS treatment approaches. Using databases like PubMed, Embase, Cochrane, Scopus, and Google Scholar, a thorough search was carried out utilizing keywords like \'MERS,\' \'MERS-CoV,\' and \'Middle East respiratory syndrome\' in conjunction with \'treatment\' or \'therapy\' from Jan 2012 to Feb 2024.
UNASSIGNED: MERS-CoV is a highly pathogenic respiratory infection that emerged in 2012 and continues to pose a significant public health threat. Despite ongoing efforts to control the spread of MERS-CoV, there is currently no specific antiviral treatment available. While many agents have been tested both in vivo and in vitro, none of them have been thoroughly examined in extensive clinical trials. Only case reports, case series, or cohort studies have been made available as clinical studies. However, there is a limited number of randomized-controlled trials. Because cases are irregular and sporadic, conducting a large prospective randomized trials for establishing an efficacious treatment might be difficult.

UNASSIGNED: Mitigating the spread of infectious diseases is of paramount concern for societal safety, necessitating the development of effective intervention measures. Epidemic simulation is widely used to evaluate the efficacy of such measures, but realistic simulation environments are crucial for meaningful insights. Despite the common use of contact-tracing data to construct realistic networks, they have inherent limitations. This study explores reconstructing simulation networks using link prediction methods as an alternative approach.
UNASSIGNED: The primary objective of this study is to assess the effectiveness of intervention measures on the reconstructed network, focusing on the 2015 MERS-CoV outbreak in South Korea. Contact-tracing data were acquired, and simulation networks were reconstructed using the graph autoencoder (GAE)-based link prediction method. A scale-free (SF) network was employed for comparison purposes. Epidemic simulations were conducted to evaluate three intervention strategies: Mass Quarantine (MQ), Isolation, and Isolation combined with Acquaintance Quarantine (AQ + Isolation).
UNASSIGNED: Simulation results showed that AQ + Isolation was the most effective intervention on the GAE network, resulting in consistent epidemic curves due to high clustering coefficients. Conversely, MQ and AQ + Isolation were highly effective on the SF network, attributed to its low clustering coefficient and intervention sensitivity. Isolation alone exhibited reduced effectiveness. These findings emphasize the significant impact of network structure on intervention outcomes and suggest a potential overestimation of effectiveness in SF networks. Additionally, they highlight the complementary use of link prediction methods.
UNASSIGNED: This innovative methodology provides inspiration for enhancing simulation environments in future endeavors. It also offers valuable insights for informing public health decision-making processes, emphasizing the importance of realistic simulation environments and the potential of link prediction methods.

Nanobodies, single-domain antibodies derived from variable domain of camelid or shark heavy-chain antibodies, have unique properties with small size, strong binding affinity, easy construction in versatile formats, high neutralizing activity, protective efficacy, and manufactural capacity on a large-scale. Nanobodies have been arisen as an effective research tool for development of nanobiotechnologies with a variety of applications. Three highly pathogenic coronaviruses (CoVs), SARS-CoV-2, SARS-CoV, and MERS-CoV, have caused serious outbreaks or a global pandemic, and continue to post a threat to public health worldwide. The viral spike (S) protein and its cognate receptor-binding domain (RBD), which initiate viral entry and play a critical role in virus pathogenesis, are important therapeutic targets. This review describes pathogenic human CoVs, including viral structures and proteins, and S protein-mediated viral entry process. It also summarizes recent advances in development of nanobodies targeting these CoVs, focusing on those targeting the S protein and RBD. Finally, we discuss potential strategies to improve the efficacy of nanobodies against emerging SARS-CoV-2 variants and other CoVs with pandemic potential. It will provide important information for rational design and evaluation of therapeutic agents against emerging and reemerging pathogens.

As of December 2022, 2603 laboratory-identified Middle East respiratory syndrome coronavirus (MERS-CoV) infections and 935 associated deaths, with a mortality rate of 36%, had been reported to the World Health Organization (WHO). However, there are still no vaccines for MERS-CoV, which makes the prevention and control of MERS-CoV difficult. In this study, we generated two DNA vaccine candidates by integrating MERS-CoV Spike (S) gene into a replicating Vaccinia Tian Tan (VTT) vector. Compared to homologous immunization with either vaccine, mice immunized with DNA vaccine prime and VTT vaccine boost exhibited much stronger and durable humoral and cellular immune responses. The immunized mice produced robust binding antibodies and broad neutralizing antibodies against the EMC2012, England1 and KNIH strains of MERS-CoV. Prime-Boost immunization also induced strong MERS-S specific T cells responses, with high memory and poly-functional (CD107a-IFN-γ-TNF-α) effector CD8+ T cells. In conclusion, the research demonstrated that DNA-Prime/VTT-Boost strategy could elicit robust and balanced humoral and cellular immune responses against MERS-CoV-S. This study not only provides a promising set of MERS-CoV vaccine candidates, but also proposes a heterologous sequential immunization strategy worthy of further development.