Middle Eastern Respiratory Syndrome Coronavirus Research Articles

Mannose-specific plant and microbial lectins as antiviral agents: A review.

Lectins are non-immunological carbohydrate-binding proteins classified on the basis oftheir structure, origin, and sugar specificity. The binding specificity of such proteins with the surface glycan moiety determines their activity and clinical applications. Thus, lectins hold great potential as diagnostic and drug discovery agents and as novel biopharmaceutical products. In recent years, significant advancements have been made in understanding plant and microbial lectins as therapeutic agents against various viral diseases. Among them, mannose-specific lectins have being proven aspromising antiviral agents against a variety of viruses, such as HIV,Influenza, Herpes, Ebola, Hepatitis, Severe Acute Respiratory Syndrome Coronavirus-1 (SARS-CoV-1), Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) and most recent Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The binding of mannose-binding lectins (MBLs) from plants and microbes to high-mannose containing N-glycans (which may be simple or complex) of glycoproteins found on the surface of viruses has been found to be highly specific and mainly responsible for their antiviral activity. MBLs target various steps in the viral life cycle, including viral attachment, entry and replication. The present review discusses the brief classification and structure of lectins along with antiviral activity of various mannose-specific lectins from plants and microbial sources and their diagnostic and therapeutic applications against viral diseases.

One for all-human kidney Caki-1 cells are highly susceptible to infection with corona- and other respiratory viruses.

In vitro investigations of host-virus interactions are reliant on suitable cell and tissue culture models. Results are only as good as the model they are generated in. However, choosing cell models for in vitro work often depends on availability and previous use alone. Despite the vast increase in coronavirus research over the past few years, scientists are still heavily reliant on: non-human, highly heterogeneous or not fully differentiated, or naturally unsusceptible cells requiring overexpression of receptors and other accessory factors. Complex primary or stem cell models are highly representative of human tissues but are expensive and time-consuming to develop and maintain with limited suitability for high-throughput experiments.Using tissue-specific expression patterns, we identified human kidney cells as an ideal target for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and broader coronavirus infection. We show the use of the well-characterized human kidney cell line Caki-1 for infection with three human coronaviruses (hCoVs): Betacoronaviruses SARS-CoV-2 and Middle Eastern respiratory syndrome coronavirus and Alphacoronavirus hCoV 229E. Caki-1 cells show equal or superior susceptibility to all three coronaviruses when compared to other commonly used cell lines for the cultivation of the respective virus. Antibody staining against SARS-CoV-2 N protein shows comparable replication rates. A panel of 26 custom antibodies shows the location of SARS-CoV-2 proteins during replication using immunocytochemistry. In addition, Caki-1 cells were found to be susceptible to two other human respiratory viruses, influenza A virus and respiratory syncytial virus, making them an ideal model for cross-comparison for a broad range of respiratory viruses. IMPORTANCE Cell lines remain the backbone of virus research, but results are only as good as their originating model. Despite increased research into human coronaviruses following the COVID-19 pandemic, researchers continue to rely on suboptimal cell line models of: non-human origin, incomplete differentiation, or lacking active interferon responses. We identified the human kidney Caki-1 cell line as a potential target for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This cell line could be shown to be infectable with a wide range of coronaviruses including common cold virus hCoV-229E, epidemic virus MERS-CoV, and SARS-CoV-2 as well as other important respiratory viruses influenza A virus and respiratory syncytial virus. We could show the localization of 26 SARS-CoV-2 proteins in Caki-1 cells during natural replication and the cells are competent of forming a cellular immune response. Together, this makes Caki-1 cells a unique tool for cross-virus comparison in one cell line.

MULTICOMPARTMENTAL ANALYSIS OF MIDDLE EASTERN RESPIRATORY SYNDROME CORONAVIRUS MODEL UNDER FRACTIONAL OPERATOR WITH NEXT-GENERATION MATRIX METHODS

Deterministic and fractional properties of an epidemic model for the dynamics of the Middle Eastern respiratory syndrome coronavirus (MERS-COV) with various infection stages are proposed in this study whose aim is to show via a mathematical model the transmission of MERS-COV between humans and camels, which are suspected to be the primary source of infection. The mathematical aspects together with biological feasibility of MERS-COV model are provided. The basic reproduction number [Formula: see text] has been calculated by using the next-generation matrix. With the help of [Formula: see text], we show the local and global stability analysis of the proposed model. Analysis of sensitivity for the threshold number is performed to understand the most sensitive parameter. Moreover, the concepts of strength number and second-order derivative of the Lyapunov function have been utilized for the waves detection. By using the concept of fixed point approach for the model, concerning if it really exists or not, we prove the existence and uniqueness results for the proposed model. The numerical solutions are obtained with the help of well-known fractional Adams–Bashforth technique. For the approximate solution, with the help of Runge–Kutta technique of order four, we accomplish the numerical simulations to support our analytical outcomes which are believed to have an effective impact on developing preventive measures for MERS-CoV, including disease control as well as prevention of spread and transmission in related populations.

Modeling the epidemic trend of middle eastern respiratory syndrome coronavirus with optimal control.

Since the outbreak of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012 in the Middle East, we have proposed a deterministic theoretical model to understand its transmission between individuals and MERS-CoV reservoirs such as camels. We aim to calculate the basic reproduction number ($ \mathcal{R}_{0} $) of the model to examine its airborne transmission. By applying stability theory, we can analyze and visualize the local and global features of the model to determine its stability. We also study the sensitivity of $ \mathcal{R}_{0} $ to determine the impact of each parameter on the transmission of the disease. Our model is designed with optimal control in mind to minimize the number of infected individuals while keeping intervention costs low. The model includes time-dependent control variables such as supportive care, the use of surgical masks, government campaigns promoting the importance of masks, and treatment. To support our analytical work, we present numerical simulation results for the proposed model.

Characterization and comparison of novel adjuvants for a prefusion clamped MERS vaccine.

Various chemical adjuvants are available to augment immune responses to non-replicative, subunit vaccines. Optimized adjuvant selection can ensure that vaccine-induced immune responses protect against the diversity of pathogen-associated infection routes, mechanisms of infectious spread, and pathways of immune evasion. In this study, we compare the immune response of mice to a subunit vaccine of Middle Eastern respiratory syndrome coronavirus (MERS-CoV) spike protein, stabilized in its prefusion conformation by a proprietary molecular clamp (MERS SClamp) alone or formulated with one of six adjuvants: either (i) aluminium hydroxide, (ii) SWE, a squalene-in-water emulsion, (iii) SQ, a squalene-in-water emulsion containing QS21 saponin, (iv) SMQ, a squalene-in-water emulsion containing QS21 and a synthetic toll-like receptor 4 (TLR4) agonist 3D-6-acyl Phosphorylated HexaAcyl Disaccharide (3D6AP); (v) LQ, neutral liposomes containing cholesterol, 1.2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and QS21, (vi) or LMQ, neutral liposomes containing cholesterol, DOPC, QS21, and 3D6AP. All adjuvanted formulations induced elevated antibody titers which where greatest for QS21-containing formulations. These had elevated neutralization capacity and induced higher frequencies of IFNƔ and IL-2-producing CD4+ and CD8+ T cells. Additionally, LMQ-containing formulations skewed the antibody response towards IgG2b/c isotypes, allowing for antibody-dependent cellular cytotoxicity. This study highlights the utility of side-by-side adjuvant comparisons in vaccine development.

A platform technology for generating subunit vaccines against diverse viral pathogens.

The COVID-19 pandemic response has shown how vaccine platform technologies can be used to rapidly and effectively counteract a novel emerging infectious disease. The speed of development for mRNA and vector-based vaccines outpaced those of subunit vaccines, however, subunit vaccines can offer advantages in terms of safety and stability. Here we describe a subunit vaccine platform technology, the molecular clamp, in application to four viruses from divergent taxonomic families: Middle Eastern respiratory syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), Lassa virus (LASV) and Nipah virus (NiV). The clamp streamlines subunit antigen production by both stabilising the immunologically important prefusion epitopes of trimeric viral fusion proteins while enabling purification without target-specific reagents by acting as an affinity tag. Conformations for each viral antigen were confirmed by monoclonal antibody binding, size exclusion chromatography and electron microscopy. Notably, all four antigens tested remained stable over four weeks of incubation at 40°C. Of the four vaccines tested, a neutralising immune response was stimulated by clamp stabilised MERS-CoV spike, EBOV glycoprotein and NiV fusion protein. Only the clamp stabilised LASV glycoprotein precursor failed to elicit virus neutralising antibodies. MERS-CoV and EBOV vaccine candidates were both tested in animal models and found to provide protection against viral challenge.

Immune determinants of chronic sequelae after respiratory viral infection.

The acute effects of various respiratory viral infections have been well studied, with extensive characterization of the clinical presentation as well as viral pathogenesis and host responses. However, over the course of the recent COVID-19 pandemic, the incidence and prevalence of chronic sequelae after acute viral infections have become increasingly appreciated as a serious health concern. Post-acute sequelae of COVID-19, alternatively described as "long COVID-19," are characterized by symptoms that persist for longer than 28 days after recovery from acute illness. Although there exists substantial heterogeneity in the nature of the observed sequelae, this phenomenon has also been observed in the context of other respiratory viral infections including influenza virus, respiratory syncytial virus, rhinovirus, severe acute respiratory syndrome coronavirus, and Middle Eastern respiratory syndrome coronavirus. In this Review, we discuss the various sequelae observed following important human respiratory viral pathogens and our current understanding of the immunological mechanisms underlying the failure of restoration of homeostasis in the lung.

Transmission dynamic and backward bifurcation of Middle Eastern respiratory syndrome coronavirus

Middle East respiratory syndrome coronavirus (MERS-CoV) remains an emerging disease threat with regular human cases on the Arabian Peninsula driven by recurring camels to human transmission events. In this paper, we present a new deterministic model for the transmission dynamics of (MERS-CoV). In order to do this, we develop a model formulation and analyze the stability of the proposed model. The stability conditions are obtained in term of R0, we find those conditions for which the model become stable. We discuss basic reproductive number R0 along with sensitivity analysis to show the impact of every epidemic parameter. We show that the proposed model exhibits the phenomena of backward bifurcation. Finally, we show the numerical simulation of our proposed model for supporting our analytical work. The aim of this work is to show via mathematical model the transmission of MERS-CoV between humans and camels, which are suspected to be the primary source of infection.

Cross-Reactive Antibodies to SARS-CoV-2 and MERS-CoV in Pre-COVID-19 Blood Samples from Sierra Leoneans.

Many countries in sub-Saharan Africa have experienced lower COVID-19 caseloads and fewer deaths than countries in other regions worldwide. Under-reporting of cases and a younger population could partly account for these differences, but pre-existing immunity to coronaviruses is another potential factor. Blood samples from Sierra Leonean Lassa fever and Ebola survivors and their contacts collected before the first reported COVID-19 cases were assessed using enzyme-linked immunosorbent assays for the presence of antibodies binding to proteins of coronaviruses that infect humans. Results were compared to COVID-19 subjects and healthy blood donors from the United States. Prior to the pandemic, Sierra Leoneans had more frequent exposures than Americans to coronaviruses with epitopes that cross-react with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), SARS-CoV, and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). The percentage of Sierra Leoneans with antibodies reacting to seasonal coronaviruses was also higher than for American blood donors. Serological responses to coronaviruses by Sierra Leoneans did not differ by age or sex. Approximately a quarter of Sierra Leonian pre-pandemic blood samples had neutralizing antibodies against SARS-CoV-2 pseudovirus, while about a third neutralized MERS-CoV pseudovirus. Prior exposures to coronaviruses that induce cross-protective immunity may contribute to reduced COVID-19 cases and deaths in Sierra Leone.

Evaluation of mobile real-time polymerase chain reaction tests for the detection of severe acute respiratory syndrome coronavirus 2

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), calls for prompt and accurate diagnosis and rapid turnaround time for test results to limit transmission. Here, we evaluated two independent molecular assays, the Biomeme SARS-CoV-2 test, and the Precision Biomonitoring TripleLock SARS-CoV-2 test on a field-deployable point-of-care real-time PCR instrument, Franklin three9, in combination with Biomeme M1 Sample Prep Cartridge Kit for RNA 2.0 (M1) manual extraction system for rapid, specific, and sensitive detection of SARS-COV-2 in cell culture, human, and animal clinical samples. The Biomeme SARS-CoV-2 assay, which simultaneously detects two viral targets, the orf1ab and S genes, and the Precision Biomonitoring TripleLock SARS-CoV-2 assay that targets the 5′ untranslated region (5′ UTR) and the envelope (E) gene of SARS-CoV-2 were highly sensitive and detected as low as 15 SARS-CoV-2 genome copies per reaction. In addition, the two assays were specific and showed no cross-reactivity with Middle Eastern respiratory syndrome coronavirus (MERS-CoV), infectious bronchitis virus (IBV), porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis (TGE) virus, and other common human respiratory viruses and bacterial pathogens. Also, both assays were highly reproducible across different operators and instruments. When used to test animal samples, both assays equally detected SARS-CoV-2 genetic materials in the swabs from SARS-CoV-2-infected hamsters. The M1 lysis buffer completely inactivated SARS-CoV-2 within 10 min at room temperature enabling safe handling of clinical samples. Collectively, these results show that the Biomeme and Precision Biomonitoring TripleLock SARS-CoV-2 mobile testing platforms could reliably and promptly detect SARS-CoV-2 in both human and animal clinical samples in approximately an hour and can be used in remote areas or health care settings not traditionally serviced by a microbiology laboratory.

A systematic review on the efficacies and therapeutic interventions of homoeopathic medicines in combating viral disorders with implications in the currently undergoing homoeopathic treatment efforts of SARS-CoV-2 infection (COVID-19)

The prevalence of Severe Acute Respiratory Syndrome- Corona Virus-2 (SARS-CoV-2) has undergone a historic transition from December 2019 to June 2020. Under the current circumstances, SARS-CoV-2 has become a key problem for the public health and economic steadiness of the global fraternity. Based on ample evidences from the global epidemiology of SARS-CoV-2 and MERS-CoV (Middle Eastern Respiratory Syndrome- Corona virus) scientists and physicians strappingly consider these viruses share structural and functional similarities of selected biologically active enzymes namely, 3CLpro, PLpro and RdRp. Ultra-diluted homoeopathic medicine has the legacy to combat infectious as well as viral diseases since last two centuries. Thus, a systematic review on existing antiviral homoeopathic therapies was done in the current study and the need of appropriate clinical validation with proper in vitro as well as in vivo studies prior to make clinical endorsements in treating Covid-19 patients with homoeopathic medicines has been explained. A brief summary of the currently undergoing or recently completed homoeopathic treatments of COVID-19 has also been provided to attract many more similar homoeopathic treatment attempts to combat COVID-19.

Modeling the transmission dynamics of middle eastern respiratory syndrome coronavirus with the impact of media coverage

Middle East respiratory syndrome coronavirus has been persistent in the Middle East region since 2012. In this paper, we propose a deterministic mathematical model to investigate the effect of media coverage on the transmission and control of Middle Eastern respiratory syndrome coronavirus disease. In order to do this we develop model formulation. Basic reproduction number R0 will be calculated from the model to assess the transmissibility of the (MERS-CoV). We discuss the existence of backward bifurcation for some range of parameters. We also show stability of the model to figure out the stability condition and impact of media coverage. We show a special case of the model for which the endemic equilibrium is globally asymptotically stable. Finally all the theoretical results will be verified with the help of numerical simulation for easy understanding.

Prevalence of posttraumatic stress disorder after infectious disease pandemics in the twenty-first century, including COVID-19: a meta-analysis and systematic review.

Pandemics have become more frequent and more complex during the twenty-first century. Posttraumatic stress disorder (PTSD) following pandemics is a significant public health concern. We sought to provide a reliable estimate of the worldwide prevalence of PTSD after large-scale pandemics as well as associated risk factors, by a systematic review and meta-analysis. We systematically searched the MedLine, Embase, PsycINFO, Web of Science, CNKI, WanFang, medRxiv, and bioRxiv databases to identify studies that were published from the inception up to August 23, 2020, and reported the prevalence of PTSD after pandemics including sudden acute respiratory syndrome (SARS), H1N1, Poliomyelitis, Ebola, Zika, Nipah, Middle Eastern respiratory syndrome coronavirus (MERS-CoV), H5N1, and coronavirus disease 2019 (COVID-19). A total of 88 studies were included in the analysis, with 77 having prevalence information and 70 having risk factors information. The overall pooled prevalence of post-pandemic PTSD across all populations was 22.6% (95% confidence interval (CI): 19.9–25.4%, I2: 99.7%). Healthcare workers had the highest prevalence of PTSD (26.9%; 95% CI: 20.3–33.6%), followed by infected cases (23.8%: 16.6–31.0%), and the general public (19.3%: 15.3–23.2%). However, the heterogeneity of study findings indicates that results should be interpreted cautiously. Risk factors including individual, family, and societal factors, pandemic-related factors, and specific factors in healthcare workers and patients for post-pandemic PTSD were summarized and discussed in this systematic review. Long-term monitoring and early interventions should be implemented to improve post-pandemic mental health and long-term recovery.

Neurotropism of SARS-CoV 2 and others Coronavirus in Children: Mechanisms and Clinical Manifestations

Neurotropism of SARS-CoV 2 and others Coronavirus in Children: Mechanisms and Clinical Manifestations

Preliminary Epidemiological Investigation of SARS-CoV-2 and Risk Factors Associated with Infection in Tarhouna, Libya

Background: During the last couple of years, the emerging and re-emerging viral diseases have been spilled over and were considered of great international concern, Severe Acute Respiratory Syndrome (SARS), Middle Eastern Respiratory Syndrome Corona virus (MERS-CoV), Ebola virus disease and Severe Acute Respiratory distress Syndrome (SARS-CoV-2). SARS-CoV-2, the virus that causes corona virus disease 2019 (COVID-19), has spread rapidly around the world since emerging in Wuhan, China, in late 2019. Objectives: The study was conducted to investigate the epidemiological situation of COVID-19 and risk factors associated with SRAS-CoV-2 infection in Tarhouna city. Materials and Methods: The cross-sectional study was conducted to investigate the epidemiological situation of COVID-19 and study the risk factors (age, gender, history of contact and comorbidity condition) associated with infection in the city of Tarhouna from December 2020 to Jan 2021. All data were entered into the Microsoft Excel spreadsheet and coded for analysis. Influence of variables like age, gender, comorbidity and history of contact on infection was calculated. A descriptive statistical analysis was performed to analyze the epidemiological characteristics of the confirmed cases of COVID-19 using SPSS version 22. For each proportion the percent and 95% confidence interval (CI) were calculated. Chi square test was used to investigate the level of association among variables at the significance level of p<0.05. Results: The present study reported 540 confirmed cases of COVID-19 screened by RT.PCR. The result showed the statistical significant (.001) at p < 0.05 among four age categories (≤19 year 5.50%, 20-39 year 42.41%, 40-59 year 48.30% and ≥60 year 4.62%). Significantly (P=.04), the gender influence on infection rate of SARS-CoV-2 amongst target population. The infection rate was estimated to be 70.74% (95% CI: 66.90%-4.58%) and 29.50% (95% CI: 25.42%-33.10%) in male and female respectively. Our results reported no statistical difference (P=.09) among comorbidity and non-comorbidity cases. It well known that the comorbidities patients are considered most risk group. Comparatively, the infection was found to be higher in history contact 92.7% (95% CI: 90.59%-94.96%) than non-contact 7.2% (95% CI: 5.04%-9.41%). unexpectedly, the infection was estimated to be 72.59% (95% CI: 68.83%-76.35%) and 27.27% (95% CI: 23.65%-31.17%) among asymptomatic and symptomatic patients respectively. Conclusion: This study is the first in the city of Tarhuona to provide information on epidemiological characterization of COVID pandemic in this city. The study emphasizes the significant effects of older age, male gender and underling diseases on the risk of mortality among COVID-19 patients. In spite, we excluded risk factors that constituted laboratory findings, vital signs or symptoms and silent cases of COVID-19, clearly that, asymptomatic cases could be underestimated. Therefore, it is recommended to take preventative measures more seriously in the elderly patients, and asymptomatic cases that play a potential silent role in COVID-19 epidemiology, and larger scale studies are highly recommended to investigate deeply the epidemiology of this virus among Libyan population.

The Recombination Potential between SARS-CoV-2 and MERS-CoV from Cross-Species Spill-over Infections

Countries in the Middle-East (ME) are tackling two corona virus outbreaks simultaneously, Middle-Eastern Respiratory Syndrome Coronavirus (MERS-CoV) and the current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Both viruses infect the same host (humans) and the same cell (type-II alveolar cells) causing lower respiratory illnesses such as pneumonia. Molecularly, MERS-CoV and SARS-CoV-2 enter alveolar cells via spike proteins recognizing dipeptidyl peptidase-4 and angiotensin converting enzyme-II, respectively. Intracellularly, both viruses hide in organelles to generate negative RNA strands and initiate replication using very similar mechanisms. At the transcription level, both viruses utilise identical Transcription Regulatory Sequences (TRSs), which are known recombination cross-over points during replication, to transcribe genes. Using whole genome alignments of both viruses, we identify clusters of high sequence homology at ORF1a and ORF1b. Given the high recombination rates detected in SARS-CoV-2, we speculate that in co-infections recombination is feasible via TRS and/or clusters of homologies. Accordingly, here we recommend mitigation measure and testing for both MERS-CoV and SARS-CoV-2 in ME countries.

S1129 Prevalence of Liver Manifestations in Coronavirus Infection: A Population-Based Study

INTRODUCTION: Along with newly identified SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) other coronaviruses, i.e. SARS-CoV and Middle Eastern respiratory syndrome coronavirus (MERS-CoV) were associated with severe respiratory illnesses and significant mortality. Gastrointestinal symptoms were frequently reported in COVID-19 patients, however, limited data have been published on the liver manifestations associated with coronavirus infection. Our objective is to study the epidemiology of hepatic manifestations and associated mortality in patients infected with the coronavirus. METHODS: We performed a retrospective cohort study using IBM EXPLORYS, HIPPA-enabled web platform that includes over 65 million patient data, pooled from multiple healthcare systems using electronic medical records. All patients with coronavirus infection were included in the study and were categorized into two groups; abnormal and normal liver enzymes. Abnormal liver enzyme group included patients with elevated levels of either aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or both. Patient characteristics, symptoms, medications, and mortality was compared between the groups. Data were analyzed with R statistical software (RStudio, Inc. Boston, MA). RESULTS: A total of 4210 patients were infected with coronavirus of which 1740 (41%) had abnormal liver enzymes. Abnormal liver enzymes were mostly noted in elderly females with age > 65 (P < 0.0001). Abdominal pain, nausea, and vomiting were the most common presentation (P < 0.0001). Immunosuppressants or steroids were significantly associated with elevated liver enzymes (P = 0.024). Pneumonia, acute respiratory distress syndrome (ARDS), septic shock, and mortality was significantly high in abnormal liver enzyme group. There was no association with race, body mass index, hepatitis, and liver transplantation (Table). CONCLUSION: Elderly patients infected with coronavirus are at higher risk to have worse outcomes. Patients with abnormal liver enzymes were at increased risk to develop pneumonia, ARDS, and septic shock. The mortality rate in this group was significantly high. Our findings suggest that elderly patients infected with coronavirus who are on immunosuppressants or steroids are at higher risk for clinical deterioration. Further multi-center studies are needed to evaluate if hepatic function panel on the day of admission, in conjunction with other risk factors, could be used to identify high-risk patients for clinical deterioration.Table 1.: Characteristics of Patients with Coronavirus InfectionTable 2.: Characteristics of Patients with Coronavirus Infection

The unique features of SARS‐CoV‐2 transmission: Comparison with SARS‐CoV, MERS‐CoV and 2009 H1N1 pandemic influenza virus

SummaryFrom 2002 to 2019, three deadly human coronaviruses (hCoVs), severe acute respiratory syndrome coronavirus (SARS‐CoV), Middle Eastern respiratory syndrome coronavirus (MERS‐CoV) and severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) emerged to produce outbreaks of SARS, MERS and coronavirus disease 2019 (Covid‐19), respectively. All three hCoVs are members of the Betacoronavirus genus in the subfamily Orthocoronavirinae and share many similarities in virology and epidemiology. However, the pattern and scale of Covid‐19 global spread is similar to 2009 pandemic H1N1 influenza (H1N1pdm09), rather than SARS or MERS. Covid‐19 exhibits high viral shedding in the upper respiratory tract at an early stage of infection, and has a high proportion of transmission competent individuals that are pre‐symptomatic, asymptomatic and mildly symptomatic, characteristics seen in H1N1pdm09 but not in SARS or MERS. These two traits of Covid‐19 and H1N1pdm09 result in reduced efficiency in identification of transmission sources by symptomatic screening and play important roles in their ability to spread unchecked to cause pandemics. To overcome these attributes of Covid‐19 in community transmission, identifying the transmission source by testing for virus shedding and interrupting chains of transmission by social distancing and public masking are required.

Current status of antivirals and druggable targets of SARS CoV-2 and other human pathogenic coronaviruses.

Coronaviridae is a peculiar viral family, with a very large RNA genome and characteristic appearance, endowed with remarkable tendency to transfer from animals to humans. Since the beginning of the 21st century, three highly transmissible and pathogenic coronaviruses have crossed the species barrier and caused deadly pneumonia, inflicting severe outbreaks and causing human health emergencies of inconceivable magnitude. Indeed, in the past two decades, two human coronaviruses emerged causing serious respiratory illness: severe acute respiratory syndrome coronavirus (SARS-CoV-1) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV), causing more than 10,000 cumulative cases, with mortality rates of 10 % for SARS-CoV-1 and 34.4 % for MERS-CoV. More recently, the severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) has emerged in China and has been identified as the etiological agent of the recent COVID-19 pandemic outbreak. It has rapidly spread throughout the world, causing nearly 22 million cases and ∼ 770,000 deaths worldwide, with an estimated mortality rate of ∼3.6 %, hence posing serious challenges for adequate and effective prevention and treatment. Currently, with the exception of the nucleotide analogue prodrug remdesivir, and despite several efforts, there is no known specific, proven, pharmacological treatment capable of efficiently and rapidly inducing viral containment and clearance of SARS-CoV-2 infection as well as no broad-spectrum drug for other human pathogenic coronaviruses. Another confounding factor is the paucity of molecular information regarding the tendency of coronaviruses to acquire drug resistance, a gap that should be filled in order to optimize the efficacy of antiviral drugs.In this light, the present review provides a systematic update on the current knowledge of the marked global efforts towards the development of antiviral strategies aimed at coping with the infection sustained by SARS-CoV-2 and other human pathogenic coronaviruses, displaying drug resistance profiles. The attention has been focused on antiviral drugs mainly targeting viral protease, RNA polymerase and spike glycoprotein, that have been tested in vitro and/or in clinical trials as well as on promising compounds proven to be active against coronaviruses by an in silico drug repurposing approach. In this respect, novel insights on compounds, identified by structure-based virtual screening on the DrugBank database endowed by multi-targeting profile, are also reported. We specifically identified 14 promising compounds characterized by a good in silico binding affinity towards, at least, two of the four studied targets (viral and host proteins). Among which, ceftolozane and NADH showed the best multi-targeting profile, thus potentially reducing the emergence of resistant virus strains. We also focused on potentially novel pharmacological targets for the development of compounds with anti-pan coronavirus activity. Through the analysis of a large set of viral genomic sequences, the current review provides a comprehensive and specific map of conserved regions across human coronavirus proteins which are essential for virus replication and thus with no or very limited tendency to mutate. Hence, these represent key druggable targets for novel compounds against this virus family. In this respect, the identification of highly effective and innovative pharmacological strategies is of paramount importance for the treatment and/or prophylaxis of the current pandemic but potentially also for future and unavoidable outbreaks of human pathogenic coronaviruses.

Co-infection of Middle Eastern respiratory syndrome coronavirus and pulmonary tuberculosis.

Co-infection of Middle Eastern respiratory syndrome, coronavirus and tuberculosis, TB has a complex clinical entities that has estimated worldwide; mostly, in the Middle East. Clinical studies have shown that the propagation of disease is faster in (MERS-CoV) and TB co-infection compared to those of mono-infection. Clinical reports have shown that treatment of tuberculosis (TB) increase the risk of (MERS-CoV) reactivation. In this article, we propose an epidemic model to represents the Middle East respiratory syndrome coronavirus and tuberculosis (TB) co-infection. To do this, we first find the basic reproductive number and analyze the stability of the model. The stability conditions are obtained in term of the basic reproductive number. We also study the bifurcation analysis of the model, using the central manifold theory. Sensitivity of the basic reproductive number is performed to understand the most sensitive parameters. Finally, we show the feasibility of the analytical work, by numerical simulation.