Middle East Respiratory Syndrome Coronavirus Research Articles

Unraveling DPP4 Receptor Interactions with SARS-CoV-2 Variants and MERS-CoV: Insights into Pulmonary Disorders via Immunoinformatics and Molecular Dynamics.

Human coronaviruses like MERS CoV are known to utilize dipeptidyl peptidase 4 (DPP4), apart from angiotensin-converting enzyme 2(ACE2) as a potential co-receptor for viral cell entry. DPP4, the ubiquitous membrane-bound aminopeptidase, is closely associated with elevation of disease severity in comorbidities. In SARS-CoV-2, there is inadequate evidence for combination of spike protein variants with DPP4, and underlying adversity in COVID-19. To elucidate this mechanistic basis, we have investigated interaction of spike protein variants with DPP4 through molecular docking and simulation studies. The possible binding interactions between the receptor binding domain (RBD) of different spike variants of SARS-CoV-2 and DPP4 have been compared with interactions observed in the experimentally determined structure of the complex of MERS-CoV with DPP4. Comparative binding affinity confers that Delta-CoV-2: DPP4 shows close proximity with MERS-CoV:DPP4, as depicted from accessible surface area, radius of gyration and number of hydrogen bonding in the interface. Mutations in the delta variant, L452R and T478K directly participate in DPP4 interaction, enhancing DPP4 binding. E484K in alpha and gamma variants of spike protein is also found to interact with DPP4. Hence, DPP4 interaction with spike protein becomes more suitable due to mutation, especially due to L452R, T478K and E484K. Furthermore, perturbation in the nearby residues Y495, Q474 and Y489 is evident due to L452R, T478K and E484K, respectively. Virulent strains of spike protein are more susceptible to DPP4 interaction and are prone to be victimized in patients due to comorbidities. Our results will aid the rational optimization of DPP4 as a potential therapeutic target to manage COVID-19 disease severity.

Sialoglycan binding triggers spike opening in a human coronavirus

Coronavirus spike proteins mediate receptor binding and membrane fusion, making them prime targets for neutralizing antibodies. In the cases of severe acute respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus 2 and Middle East respiratory syndrome coronavirus, spike proteins transition freely between open and closed conformations to balance host cell attachment and immune evasion1–5. Spike opening exposes domain S1B, allowing it to bind to proteinaceous receptors6,7, and is also thought to enable protein refolding during membrane fusion4,5. However, with a single exception, the pre-fusion spike proteins of all other coronaviruses studied so far have been observed exclusively in the closed state. This raises the possibility of regulation, with spike proteins more commonly transitioning to open states in response to specific cues, rather than spontaneously. Here, using cryogenic electron microscopy and molecular dynamics simulations, we show that the spike protein of the common cold human coronavirus HKU1 undergoes local and long-range conformational changes after binding a sialoglycan-based primary receptor to domain S1A. This binding triggers the transition of S1B domains to the open state through allosteric interdomain crosstalk. Our findings provide detailed insight into coronavirus attachment, with possibilities of dual receptor usage and priming of entry as a means of immune escape.

Universal features of Nsp1-mediated translational shutdown by coronaviruses

Nonstructural protein 1 (Nsp1) produced by coronaviruses inhibits host protein synthesis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp1 C-terminal domain was shown to bind the ribosomal mRNA channel to inhibit translation, but it is unclear whether this mechanism is broadly used by coronaviruses, whether the Nsp1 N-terminal domain binds the ribosome, or how Nsp1 allows viral RNAs to be translated. Here, we investigated Nsp1 from SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), and Bat-Hp-CoV coronaviruses using structural, biophysical, and biochemical experiments, revealing a conserved role for the C-terminal domain. Additionally, the N-terminal domain of Bat-Hp-CoV Nsp1 binds to the decoding center of the 40S subunit, where it would prevent mRNA and eIF1A accommodation. Structure-based experiments demonstrated the importance of decoding center interactions in all three coronaviruses and showed that the same regions of Nsp1 are necessary for the selective translation of viral RNAs. Our results provide a mechanistic framework to understand how Nsp1 controls preferential translation of viral RNAs.

Bibliometric Analysis of the Publications on Middle East Respiratory Syndrome Coronavirus Published Between 2012-2022.

This study aimed to conduct a bibliometric analysis of the global scientific output related to the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) between 2012 and 2022. The Web of Science database was searched for articles on MERS-CoV published between 2012 and 2022 for bibliometric analysis. The parameters such as publication year, publication type, funding agencies, research institutions, journals, impact factors, language, and citation numbers of articles were analyzed. We included 1475 articles on MERS-CoV from 86 countries. The United States was the most published country on MERS-CoV, with 487 articles. The Saudi Ministry of Health (7.53%), King Saud bin Abdulaziz University for Health Sciences (6.92%), and The Egyptian Knowledge Bank (6.64%) were the most published institutions. The researchers who published the most on MERS-CoV were from Saudi Arabia. One thousand two hundred six funding agencies funded publications on MERS-CoV, most of which were funded by agencies from the United States. MERS-CoV remains important because no treatment and no vaccine have been found since it was first detected, and accordingly, it continues to affect the world with new outbreaks and high mortality rates. In addition, experiences with MERS-CoV during the coronavirus disease 2019 (COVID-19) pandemic have guided new research on COVID-19, so scientific interest in MERS-CoV is still ongoing.

Presence of SARS-CoV-2-like coronaviruses in bats from east coast Malaysia.

Most of the public health importance coronaviruses, such as Severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2 are likely originated from bats and spread to humans through intermediate hosts; civet cats, dromedary camel and Malayan pangolin, respectively. SARS-CoV-2-like coronaviruses were detected in Thailand, which is neighbouring with Kelantan in East Coast Malaysia. To date, there is no report on the presence of public health concerns (SARS-CoV, SARS-CoV-2 and MERS-CoV) coronaviruses in bats from Malaysia. This study was aimed to elucidate the presence of these coronaviruses in bat samples from East Coast, Malaysia. A total of hundred seventy oropharyngeal swab samples were collected from three states of East Coast Malaysia. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was conducted based on partial 3' Untranslated region (3'UTR) or ORF10 gene and the products were sequenced. The sequences were compared with all coronavirus sequences from the National Center for Biotechnology Information-GenBank (NCBI-GenBank) using NCBI-Basic Local Alignment Search Tool (NCBI-BLAST) software. A phylogenetic tree was constructed to determine the genetic relationship among the detected coronaviruses with the reference coronaviruses from the NCBI-GenBank. Our results showed that SARSCoV-2-like viruses were present in 3% (5/170) of the bats from East Coast Malaysia that have 98-99% sequence identities and are genetically related to SARS-CoV-2 from humans. This finding indicates the presence of SARS-CoV-2-like viruses in bats from East Coast Malaysia that may become a public health concern in the future.

Global Health Security

To reduce the risk and effect of sudden incidents of public health that put people at risk across national and international boundaries, it is necessary to take both preventive and reactive measures. These measures are referred to as global health security. Discussions on health security in scientific gatherings have become more prevalent in recent years after the Covid pandemic. Health security is for the whole world, irrespective of age, race, gender, or financial stability. However, it has been noted that there are many different concepts of health security, that the whole purpose of this is to accommodate only the upper-class societies. The disturbed equilibrium of the microbial world due to rapid urbanization, population increase, environmental deterioration, and the improper use of antimicrobials makes people realize the importance of health security that requires a collaborative approach focused on preparedness for any future pandemics and equal access to health care products. 
 The covid-19 pandemic has had a great influence on people’s lives and their ability to think. Now the main race is not about defence systems; it has shifted towards more and better health security and the ability to deal with any future pandemics. The coronavirus outbreak was associated with severe acute respiratory syndrome, the Middle East respiratory syndrome coronavirus outbreak in 2012, the swine flu pandemic in 2009, and the West African Ebola virus disease epidemic in 2013–2016. All these epidemics are primarily caused by the significant travel of infected people across borders. This highlights the need for global health security, which helps coordinate surveillance and policymaking. This limits disease transmission and reduces the damage.
 While infectious diseases have no limits, inadequate health systems in poor nations make them worse and more out of control. Africa and other third-world states face many problems in securing global security. The spread of infectious diseases among susceptible areas is due to inadequate public healthcare fundings, vaccine coverage, poverty, armed conflict, and climate-related disasters, which damage developing countries. This only serves to increase susceptibility to the disease. The continuous transmission of polio and measles in different parts of Africa and Asia, as well as recent Ebola outbreaks in West Africa, highlights the need to overcome this in order to stop the spread of diseases to other areas. No nation can be completely protected from the spread of diseases due to a lack of social services and a strong health infrastructure; hence, global security demands global equality and progress towards health for everyone. 
 To advance global health security in all nations, there is a need for multi-stakeholders and governance, justifiable finance through the proposed pandemic funds, and common goods for health. Future outbreaks can be efficiently managed by funding basic healthcare and enhancing the response systems. Equity in pandemic preparedness and response measures depends on high-level political commitment and global leadership irrespective of colour and gender. False contradictions between countries can be dismissed by focused investments in strengthening health emergency infrastructure, particularly through primary healthcare, ensuring that the world is better prepared to handle complex public health emergencies.

Control of emerging and re-emerging zoonotic and vector-borne diseases in countries of the Eastern Mediterranean Region

Despite improvements in the detection and control of infectious diseases, many new pathogens are emerging and re-emerging in various parts of the world. Most of these emerging and re-emerging infections are of zoonotic origin, which highlights the importance of the human–animal interface. Similarly, the rate of vector-borne diseases has increased recently due to changes in human habitats, climate change, deforestation, changes in food production practices, and increased population movement. The risk of spread of these zoonotic and vector-borne diseases is higher in the Eastern Mediterranean Region (EMR) of the World Health Organization due to its topography and geopolitical situation, fragile health systems, complex humanitarian emergencies, and, in some countries, other socioeconomic risk factors. Many countries in the region have reported outbreaks of zoonotic and vector-borne diseases over the last few decades, and some of these diseases have spread to other WHO regions as well. Avian influenza A (H5N1) and Middle East respiratory syndrome coronavirus (MERS-CoV) are among the greatest threats to global health security and both viruses are endemic in the EMR. Countries in the EMR have made significant progress toward the control of zoonotic and vector-borne diseases in recent years, and prevention, preparedness, and response capacities have been improved. However, there are still many challenges associated with the control of these diseases in the EMR, particularly in countries facing humanitarian emergencies. In this paper, we present the current situation of emerging and re-emerging infections in the EMR and discuss progress, challenges, and ways forward.

Short commentary on fractional model for Middle East Respiratory Syndrome Coronavirus on a complex heterogeneous network

Short commentary on fractional model for Middle East Respiratory Syndrome Coronavirus on a complex heterogeneous network

Interleukin 13-Induced Inflammation Increases DPP4 Abundance but Does Not Enhance Middle East Respiratory Syndrome Coronavirus Replication in Airway Epithelia.

Chronic pulmonary conditions such as asthma and chronic obstructive pulmonary disease increase the risk of morbidity and mortality during infection with the Middle East respiratory syndrome coronavirus (MERS-CoV). We hypothesized that individuals with such comorbidities are more susceptible to MERS-CoV infection due to increased expression of its receptor, dipeptidyl peptidase 4 (DPP4). We modeled chronic airway disease by treating primary human airway epithelia with the Th2 cytokine interleukin 13 (IL-13), examining how this affected DPP4 protein levels with MERS-CoV entry and replication. IL-13 exposure for 3 days led to greater DPP4 protein abundance, while a 21-day treatment raised DPP4 levels and caused goblet cell metaplasia. Surprisingly, despite this increase in receptor availability, MERS-CoV entry and replication were not significantly affected by IL-13 treatment. Our results suggest that greater DPP4 abundance is likely not the primary mechanism leading to increased MERS severity in the setting of Th2 inflammation. Transcriptional profiling analysis highlighted the complexity of IL-13-induced changes in airway epithelia, including altered expression of genes involved in innate immunity, antiviral responses, and maintenance of the extracellular mucus barrier. These data suggest that additional factors likely interact with DPP4 abundance to determine MERS-CoV infection outcomes.

Oligomeric State of β-Coronavirus Non-Structural Protein 10 Stimulators Studied by Small Angle X-ray Scattering.

The β-coronavirus family, encompassing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Severe Acute Respiratory Syndrome Coronavirus (SARS), and Middle East Respiratory Syndrome Coronavirus (MERS), has triggered pandemics within the last two decades. With the possibility of future pandemics, studying the coronavirus family members is necessary to improve knowledge and treatment. These viruses possess 16 non-structural proteins, many of which play crucial roles in viral replication and in other vital functions. One such vital protein is non-structural protein 10 (nsp10), acting as a pivotal stimulator of nsp14 and nsp16, thereby influencing RNA proofreading and viral RNA cap formation. Studying nsp10 of pathogenic coronaviruses is central to unraveling its multifunctional roles. Our study involves the biochemical and biophysical characterisation of full-length nsp10 from MERS, SARS and SARS-CoV-2. To elucidate their oligomeric state, we employed a combination of Multi-detection Size exclusion chromatography (Multi-detection SEC) with multi-angle static light scattering (MALS) and small angle X-ray scattering (SAXS) techniques. Our findings reveal that full-length nsp10s primarily exist as monomers in solution, while truncated versions tend to oligomerise. SAXS experiments reveal a globular shape for nsp10, a trait conserved in all three coronaviruses, although MERS nsp10, diverges most from SARS and SARS-CoV-2 nsp10s. In summary, unbound nsp10 proteins from SARS, MERS, and SARS-CoV-2 exhibit a globular and predominantly monomeric state in solution.

A conserved N protein nano-vaccine of COVID-19 exerts potent and cross-reactive humoral and cellular immune responses in mice.

As severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mutates continually, the current vaccines are unable to provide sufficient protection. It is important to develop a broad-spectrum vaccine with conserved antigens to prevent variant infection. Here we fused the SARS-CoV-2 N protein with Helicobacter pylori nonheme ferritin to construct a SARS-CoV-2 N-Ferritin nanoparticle vaccine. Compared with the monomer N protein, the N-Ferritin nanoparticles induced more lymph node dendritic cells in mice to trigger adoptive immunity. Following this, the N-Ferritin elicited more robust and long-lasting antibody responses, which had better cross-reactivity with the SARS-CoV N protein. It is also worth noting that higher levels of N-specific IgG and IgA were distributed in the lungs of N-Ferritin-immunized mice. Furthermore, the N-Ferritin nanoparticles also resulted higher proportion of interferon-γ+ CD8+ T cells, CD8+ Tcm cells, and T cells with cross-reactivity in SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome-related coronavirus. The conserved N-based nanoparticles could provide a promising vaccine developing strategy against SARS-CoV-2 variants and other coronaviruses.

Cancer management during the COVID-19 world pandemic.

Since 2019, the world has been experiencing an outbreak of a novel beta-coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV)-2. The worldwide spread of this virus has been a severe challenge for public health, and the World Health Organization declared the outbreak a public health emergency of international concern. As of June 8, 2023, the virus' rapid spread had caused over 767 million infections and more than 6.94 million deaths worldwide. Unlike previous SARS-CoV-1 and Middle East respiratory syndrome coronavirus outbreaks, the COVID-19 outbreak has led to a high death rate in infected patients; this has been caused by multiorgan failure, which might be due to the widespread presence of angiotensin-converting enzyme 2 (ACE2) receptors-functional receptors of SARS-CoV-2-in multiple organs. Patients with cancer may be particularly susceptible to COVID-19 because cancer treatments (e.g., chemotherapy, immunotherapy) suppress the immune system. Thus, patients with cancer and COVID-19 may have a poor prognosis. Knowing how to manage the treatment of patients with cancer who may be infected with SARS-CoV-2 is essential. Treatment decisions must be made on a case-by-case basis, and patient stratification is necessary during COVID-19 outbreaks. Here, we review the management of COVID-19 in patients with cancer and focus on the measures that should be adopted for these patients on the basis of the organs or tissues affected by cancer and by the tumor stage.

Chronicling the 3-year evolution of the COVID-19 pandemic: analysis of disease management, characteristics of major variants, and impacts on pathogenicity.

Announced on December 31, 2019, the novel coronavirus arising in Wuhan City, Hubei Province resulted in millions of cases and lives lost. Following intense tracking, coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO) in 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the cause of COVID-19 and the continuous evolution of the virus has given rise to several variants. In this review, a comprehensive analysis of the response to the pandemic over the first three-year period is provided, focusing on disease management, development of vaccines and therapeutics, and identification of variants. The transmissibility and pathogenicity of SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, and Omicron are compared. The binding characteristics of the SARS-CoV-2 spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor and reproduction numbers are evaluated. The effects of major variants on disease severity, hospitalisation, and case-fatality rates are outlined. In addition to the spike protein, open reading frames mutations are investigated. We also compare the pathogenicity of SARS-CoV-2 with SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Overall, this study highlights the strengths and weaknesses of the global response to the pandemic, as well as the importance of prevention and preparedness. Monitoring the evolution of SARS-CoV-2 is critical in identifying and potentially predicting the health outcomes of concerning variants as they emerge. The ultimate goal would be a position in which existing vaccines and therapeutics could be adapted to suit new variants in as close to real-time as possible.

Three to Six-Months Follow-Up Chest CT Findings after COVID-19 Pneumonitis, Incidence of Complications and Correlation to Different Risk Factors

Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, has become a global pandemic. As of November 19, 2020, World Health Organization stated that this disease has been found in more than 200 countries. Pathology studies have shown that COVID-19 causes injuries in multiple organs and tissues, with extensive pulmonary involvement similar to that found in other coronavirus infections (ie, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus infection). Aim of the Work to evaluate pulmonary changes on 3-6 months follow-up chest CT scans and to explore the risk factors for fibrotic-like changes in the lung in patients who recovered from COVID-19 pneumonia. Patients and Methods This was a retrospective and prospective study that included 50 patients who had Symptoms of variable degree of fever, cough, and dyspnea with RT-PCR confirmed COVID- 19 infection at Ain Shams University Hospitals referred to the Radiodiagnosis Department for HRCT chest examination. All patients were evaluated for: (I): Incidence of complications (residual fibrotic like changes in their follow up CT chest scans). (Il): Correlation to different risk factors such as (smoking, diabetes mellitus, hypertension, pre-existing pulmonary disease, pre-existing renal disease and steroid therapy). Results 56% of cases showed residual fibrotic like changes in their follow up chest CT scans while 44% of cases showed total resolution of the disease process. Smoking and old age were significant risk factors while steroid therapy decreased risk of fibrotic like change. Conclusion Twenty eight cases (56%) showed residual fibrotic like changes in their 3-6 months follow-up chest CT scan (CO-RADS III to V). Patients with older age and smokers have higher incidence of residual fibrotic like changes in their follow up chest CT scans, while patients on steroid therapy have less liability to develop fibrotic changes.

Double-antibody-based nano-biosensing system for the onsite monitoring of SARS-CoV-2 variants

The fast and reliable diagnosis of COVID-19 is the foremost priority for promoting public health interventions. Therefore, double-antibody-based immunobiosensor chips were designed, constructed, and exploited for clinical diagnosis. Gold nanoparticles/tungsten oxide/carbon nanotubes (AuNPs/WO3/CNTs) were used as the active working sensor surface to support the chemical immobilization of a mixture of SARS-CoV-2 antibodies (anti-RBD-S and anti-RBD-S-anti-Llama monoclonal antibodies). The morphology and chemical functionalization of the fabricated disposable immunochips was characterized using scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). After full assay optimization, the immunobiosensor showed a high sensitivity to detect SARS-CoV-2-S protein with limits of detection and quantification of 1.8 and 5.6 pg/mL, respectively. On the other hand, for the SARS-CoV-2 whole virus particle analysis, the detection and quantification limits were determined to be 5.7 and 17 pg/mL, respectively. The biosensor showed a highly selective response toward SARS-CoV-2, even in the presence of influenza, nontargeting human coronaviruses, and Middle East respiratory syndrome coronavirus (MERS-CoV). The immunochips exhibited distinct responses toward the variants of concern: B.1>C.36.3>Omicron> Delta> Alpha coronavirus variants. For biosensor validation, twenty-nine clinical specimens were analyzed, and the impedimetric responses were positively detected for two Delta samples, eighteen Omicron samples, and six B.1-type samples in addition to three negative samples. Eventually, the immunobiosensor was fabricated in the form of ready-to-use chips capable of sensitive detection of virus variants, especially variants of concern (VOC) and interest, in a specimen within 15 min. The chips provided instantaneous detection with the direct application of clinical samples and are considered a point-of-care device that could be used in public places and hot spots.

Pyronaridine tetraphosphate is an efficacious antiviral and anti-inflammatory active against multiple highly pathogenic coronaviruses.

Pyronaridine tetraphosphate is on the WHO Essential Medicine List for its importance as a widely available and safe treatment for malaria. We find that pyronaridine is a highly effective antiviral therapeutic across mouse models using multiple variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the highly pathogenic viruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus responsible for previous coronavirus outbreaks. Additionally, we find that pyronaridine additively combines with current COVID-19 treatments such as nirmatrelvir (protease inhibitor in Paxlovid) and molnupiravir to further inhibit SARS-CoV-2 infections. There are many antiviral compounds that demonstrate efficacy in cellular models, but few that show this level of impact in multiple mouse models and represent a promising therapeutic for the current coronavirus pandemic as well as future outbreaks as well.

Novel mono- and multivalent N-acetylneuraminic acid glycoclusters as potential broad-spectrum entry inhibitors for influenza and coronavirus infection

N-acetylneuraminic acid (Neu5Ac) is a glycan receptor of viruses spread in many eukaryotic cells. The present work aimed to design, synthesis and biological evaluation of a panel of Neu5Ac derivatives based on a cyclodextrin (CD) scaffold for targeting influenza and coronavirus membrane proteins. The multivalent Neu5Ac glycoclusters efficiently inhibited chicken erythrocyte agglutination induced by intact influenza virus in a Neu5Ac density–dependent fashion. Compared with inhibition by Neu5Ac, the multivalent inhibitor with 21 Neu5Ac residues on the primary face of the β-CD scaffold afforded 1788-fold higher binding affinity inhibition for influenza virus hemagglutinin with a dissociation constant (KD) of 3.87 × 10−7 M. It showed moderate binding affinity to influenza virus neuraminidase, but with only about one-thirtieth the potency of that with the HA protein. It also exhibited strong binding affinity to the spike protein of three human coronaviruses (severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus, and severe acute respiratory syndrome coronavirus 2), with KD values in the low micromolar range, which is about 10-time weaker than that of HA. Therefore, these multivalent sialylated CD derivatives have possible therapeutic application as broad-spectrum antiviral entry inhibitors for many viruses by targeting the Neu5Ac of host cells.

Identification of potential antiviral compounds from Egyptian Red Sea soft corals against Middle East respiratory syndrome coronavirus

The ongoing threat of Middle East respiratory syndrome coronavirus (MERS-CoV) underscores the importance of developing effective antiviral treatments. Current research was conducted to identify potential antiviral compounds from soft corals: Sinularia leptoclados, Sarcophyton ehrenbergi, Nephthea sp., Sarcophyton glaucum and Sarcophyton regulare. The antiviral activities of soft corals extracts were evaluated against MERS-CoV. Gas chromatography-mass spectrometry (GC-MS) was used to identify bioactive compounds. The molecular docking was performed to examine the identified compounds for their binding potentials towards three pathogenic factors of MERS-CoV: main protease, spike and non-structural protein 16/10 complex. The methanolic extract of soft coral Sarcophyton regulare exhibited the most promising activity with 50% inhibitory concentration (IC50) of 4.29 µg/ml and selective index (SI) of 112.2. Among the identified compounds in the active fraction, the molecular docking showed that two fatty acid esters: hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester and octadecanoic acid, 2-hydroxy-1 (hydroxymethyl) ethyl ester had promising docking scores.

The Protective Efficacy of Single-Dose Nasal Immunization with Cold-Adapted Live-Attenuated MERS-CoV Vaccine against Lethal MERS-CoV Infections in Mice.

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe diseases in humans. Camels act as intermediate hosts for MERS-CoV. Currently, no licensed vaccine is available for this virus. We have developed a potential candidate vaccine for MERS-CoV using the cold adaptation method. We cultivated the vaccine in Vero cells at temperatures as low as 22 °C. This live-attenuated vaccine virus showed high attenuation levels in transgenic mice with the MERS-CoV human receptor, dipeptidyl peptidase 4 (DPP4) (K18-hDPP4). The inoculated K18-hDPP4 mice exhibited no clinical signs such as death or body weight loss. Furthermore, no traces of infectious virus were observed when the tissues (nasal turbinate, brain, lung, and kidney) of the K18-hDPP4 mice infected with the cold-adapted vaccine strain were tested. A single intranasal dose of the vaccine administered to the noses of the K18-hDPP4 mice provided complete protection. We did not observe any deaths, body weight loss, or viral detection in the tissues (nasal turbinate, brain, lung, and kidney). Based on these promising results, the developed cold-adapted, attenuated MERS-CoV vaccine strain could be one of the candidates for human and animal vaccines.

Diketo acid inhibitors of nsp13 of SARS-CoV-2 block viral replication

For RNA viruses, RNA helicases have long been recognized to play critical roles during virus replication cycles, facilitating proper folding and replication of viral RNAs, therefore representing an ideal target for drug discovery. SARS-CoV-2 helicase, the non-structural protein 13 (nsp13) is a highly conserved protein among all known coronaviruses, and, at the moment, is one of the most explored viral targets to identify new possible antiviral agents. In the present study, we present six diketo acids (DKAs) as nsp13 inhibitors able to block both SARS-CoV-2 nsp13 enzymatic functions. Among them four compounds were able to inhibit viral replication in the low micromolar range, being active also on other human coronaviruses such as HCoV229E and MERS CoV. The experimental investigation of the binding mode revealed ATP-non-competitive kinetics of inhibition, not affected by substrate-displacement effect, suggesting an allosteric binding mode that was further supported by molecular modelling calculations predicting the binding into an allosteric conserved site located in the RecA2 domain.