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AbstractTuberculosis infection has always been a global concern for public health, and the mortality rate has increased tremendously every year. The ability of the resuscitation Mycobacterium tuberculosis(Mtb) from the dormant state is one of the major reasons for the epidemic spread of tuberculosis infection, especially latent tuberculosis infection (LTBI). The element that encourages resuscitation, RpfB (resuscitation-promoting factors B), is mostly in charge of bringing Mtbout of slumber. This reason makes RpfB a promising target for developing tuberculosis drugs because of the effects of latent tuberculosis. Therefore, this work was executed using a computational three-level screening of the Selleckhem antibiotics database consisting of 462 antibiotics against the ligand binding region of the RpfB protein, followed by an estimation of binding free energy for ideal identification and confirmation of potential RpfB inhibitor. Subsequently, three antibiotic drug molecules, i.e., Amikacin hydrate (−66.87 kcal/mol), Isepamicin sulphate (−60.8 kcal/mol), and Bekanamycin (−46.89 kcal/mol), were selected on the basis of their binding free energy value for further computational studies in comparison to reference ligand, 4-benzoyl-2-nitrophenyl thiocyanate (NPT7). Based on the intermolecular interaction profiling, 200 ns molecular dynamic simulation (MD), post-simulation analysis and principal component analysis (PCA), the selected antibiotics showed substantial stability with the RpfB protein compared to the NPT7 inhibitor. Conclusively based on the computational results, the preferred drugs can be potent inhibitors of the RpfB protein, which can be further validated using in vivoresearch and in vitroenzyme inhibition to understand their therapeutic activity against tuberculosis infection.Communicated by Ramaswamy H. Sarma

Middle East Respiratory Syndrome Coronavirus is a highly pathogenic virus that poses a significant threat to public health. The purpose of this study is to develop and characterize novel mouse monoclonal antibodies targeting the spike protein S1 subunit of the Middle East Respiratory Syndrome Corona Virus (MERS-CoV). In this study, three mouse monoclonal antibodies (mAbs) against MERS-CoV were generated and characterized using hybridoma technology. The mAbs were evaluated for their reactivity and neutralization activity. The mAbs were generated through hybridoma technology by the fusion of myeloma cells and spleen cells from MERS-CoV-S1 immunized mice. The resulting hybridomas were screened for antibody production using enzyme-linked immunosorbent assays (ELISA). ELISA results demonstrated that all three mAbs exhibited strong reactivity against the MERS-CoV S1-antigen. Similarly, dot-ELISA revealed their ability to specifically recognize viral components, indicating their potential for diagnostic applications. Under non-denaturing conditions, Western blot showed the mAbs to have robust reactivity against a specific band at 116 KDa, corresponding to a putative MERS-CoV S1-antigen. However, no reactive bands were observed under denaturing conditions, suggesting that the antibodies recognize conformational epitopes. The neutralization assay showed no in vitroreactivity against MERS-CoV. This study successfully generated three mouse monoclonal antibodies against MERS-CoV using hybridoma technology. The antibodies exhibited strong reactivity against MERS-CoV antigens using ELISA and dot ELISA assays. Taken together, these findings highlight the significance of these mAbs for potential use as valuable tools for MERS-CoV research and diagnosis (community and field-based surveillance and viral antigen detection).

AbstractRNA-dependent RNA polymerase (RdRp) is considered a potential drug target for dengue virus (DENV) inhibition and has attracted attention in antiviral drug discovery. Here, we screened 121 natural compounds from Litsea cubebaagainst DENV RdRp using various approaches of computer-based drug discovery. Notably, we identified four potential compounds (Ushinsunine, Cassameridine, (+)-Epiexcelsin, (−)-Phanostenine) with good binding scores and allosteric interactions with the target protein. Moreover, molecular dynamics simulation studies were done to check the conformational stability of the complexes under given conditions. Additionally, we performed post-simulation analysis to find the stability of potential drugs in the target protein. The findings suggest Litsea cubeba-derived phytomolecules as a therapeutic solution to control DENV infection.Communicated by Ramaswamy H. Sarma

AbstractThe majority of the world population (around 25%) has latent Mycobacterium tuberculosis (Mtb) infection, among which only 5–10% of individuals develop active tuberculosis (TB), and 90–95% continue to have latent tuberculosis infection. This makes it the biggest global health concern. It has been reported that the resuscitation-promoting factor B (RpfB) is an exciting potential target for tuberculosis drug discovery due to its significant role in the reactivation of latent TB infection to an active infection. Several attempts have been made to investigate potential inhibitors against RpfB utilizing in-silico approaches. The present study also utilized a computational approach to investigate microbially derived natural compounds against the Mtb RpfB protein which is a very cost-effective This evaluation used structure-based virtual screening (SBVS), drug-likeness profiling, molecular docking, molecular dynamics simulation, and free-binding energy calculations. Six potential natural compounds, viz. Cyclizidine I, Boremexin C, Xenocoumacin 2, PM-94128, Cutinostatin B, and (+)1-O-demethylvariecolorquinone A were selected, which displayed a potential binding affinity between −52.39 and −60.87 Kcal/mol MMGBSA score and docking energy between −7.307 Kcal/mol to −6.972 Kcal/mol. All the complexes showed acceptable stability (<2.7 Å RMSD) during 100 ns MD simulation time except the RpfB protein-xenocoumacin 2 complex. This result exhibited that the selected compounds have high efficiency in inhibiting the Mtb RpfB and can be taken into account for additional in vitroand in vivoexperimental validation.Communicated by Ramaswamy H. Sarma

Background: COVID-19 vaccination effectively decreased hospitalization and mortality during the surge of infections with the SARS-CoV-2 Omicron variant. However, patients infected with the Omicron variant who did not receive a third COVID-19 vaccine booster often required critical care unit (CCU) admission. The CCU bed utilization of COVID-19 posed a worldwide burden. The decision to stop isolation of patients with COVID-19 in CCUs is challenging, given the variable viral shedding in heterogeneous patient populations. Rapid antigen detection tests (RADTs) have been used in communities to determine patients’ infectiousness and need for quarantine. However, the use of RADTs in the de-isolation of CCU patients had not been studied. Methods: Serial RADTs, RT-PCR and viral culturing were performed in a case series of three critically ill patients infected with Omicron variants. Results: The duration of infectious viral shedding was 13–46 days post symptom onset (PSO). Concordant negative results were observed between RADTs and viral cultures on D32 PSO in case 1; D13 and D15 PSO in case 2; and D46 and D48 PSO in case 3. In addition, concordant positive results were found between RADTs and viral cultures on D35 PSO in case 2. Significant agreement was observed between RADT and viral culture findings (kappa statistic = 1.0 and p-value = 0.014). Conclusion: Given their high positive predictive value with respect to positive viral cultures, RADTs may be a promising and practical tool for ending isolation of patients with COVID-19 and decreasing the burden of CCU bed utilization. Future studies are necessary to confirm our findings.

Background: The unusual pneumonia outbreak that originated in the city of Wuhan, China in December 2019 was found to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or COVID-19. Methods: In this work, we have performed an in silico design and prediction of potential siRNAs based on genetic diversity and recombination patterns, targeting various genes of SARS-CoV-2 for antiviral therapeutics. We performed extensive sequence analysis to analyze the genetic diversity and phylogenetic relationships, and to identify the possible source of virus reservoirs and recombination patterns, and the evolution of the virus as well as we designed the siRNAs which can be used as antivirals against SARS-CoV-2. Results: The sequence analysis and phylogenetic relationships indicated high sequence identity and closed clusters with many types of coronavirus. In our analysis, the full-genome of SARS-CoV-2 showed the highest sequence (nucleotide) identity with SARS-bat-ZC45 (87.7%). The overall sequence identity ranged from 74.3% to 87.7% with selected SARS viruses. The recombination analysis indicated the bat SARS virus is a potential recombinant and serves as a major and minor parent. We have predicted 442 siRNAs and finally selected only 19 functional, and potential siRNAs. Conclusion: The siRNAs were predicted and selected based on their greater potency and specificity. The predicted siRNAs need to be validated experimentally for their effective binding and antiviral activity.

Background: Viruses are known as the major causative agents for infectious diseases globally. The coronaviruses are one of the serious pathogens to cause serious diseases in humans. Recently identified SARSCoV- 2 from Wuhan City, China, has emerged as a serious threat to human health and caused a global pandemic. Bats have been confirmed as a primary source of infection. The vaccination of the human population and animals serving as a potential reservoir is a straightforward strategy to control the transmission of any pathogen to humans. Natural products from many herbal plants are well known to have novel antiviral properties and evaluated against various viral diseases. There are many alkaloids that have shown to be effective against coronaviruses. Methods: Recently, the antiviral efficacy of natural alkaloids known as Homoharringtonine (HTT) and Emetine has been evaluated and provided promising results against coronaviruses, including SARS-CoVs. These alkaloids may be very useful and can be used as antivirals against SARS-CoV-2 because they have already been reported to inhibit the replication of SASRS-CoV and other viruses in cell lines. Conclusion: This review specifically focuses on the recent findings of these alkaloids against coronaviruses and possible treatment options for SARS-CoV-2. It is expected that natural products as alkaloids from herbal plants could be considered as novel and valuable candidates for the new antiviral drugs against SARS-CoV-2.

Introduction: Influenza infection poses a significant public health threat. The core for disease prevention and control relies on strengthened surveillance activities, particularly in Saudi Arabia, the country that hosts the largest annual mass gathering event worldwide. This study aimed to assess the molecular and seasonal pattern of influenza virus subtypes in western Saudi Arabia to inform policy decisions on influenza vaccine. Methods: This cross-sectional study was conducted at King Abdulaziz Medical City, western Saudi Arabia. Medical records and surveillance database of laboratory-confirmed influenza cases were reviewed from October 2015 to 2019. A panel of real-time polymerase chain reactions was performed to detect influenza A and B. Extracted RNA from a subset of positive samples was used to determine influenza A subtypes and influenza B lineages. Results: This study included a total of 1928 patients with laboratory-confirmed influenza infections. Influenza peaks were observed in October each season, with variant predominant strains. Influenza virus subtypes co-circulate with no reports of co-infection. Influenza A(H3N2) was reported in 42% of the cases, then influenza B (30.7%) and influenza A(H1N1)pdm09 (27.3%). Healthcare workers represented 9.4% of the cases. One-third of the cases (30.4%) were admitted to the hospital with a median admission duration of 4 days. The influenza B viruses were subtyped in 218 cases. Victoria lineage was predominant (64.1%) in 2015 and 2016; however, Yamagata was predominant in the next two consecutive seasons (94.4% and 85.4%, respectively). Conclusion: The burden due to influenza B may be underestimated with an observed vaccine mismatch. A quadrivalent influenza vaccine is recommended to reduce the health impact associated with influenza B infections. Molecular surveillance of the influenza viruses should be enhanced continuously for a better understanding of the influenza activity and assessment of vaccine effectiveness.

Background: Human coronaviruses (HCoV) are common viruses and known to be associated with respiratory diseases, including pneumonia. Currently, seven human coronaviruses have been identified and known to cause upper and lower respiratory infections as well as nosocomial viral infections in humans. The bats, palm civets, and camels are identified as the reservoir of human coronaviruses. In 2002-2003, the emergence of SARS-CoV resulted in an outbreak and led towards the more awareness and importance of scientific research and medical urgency. Methods: The recently identified SARS-CoV-2 was identified from the seafood market of the city Wuhan, China, in December 2019 and caused a global pandemic. This virus has now spread to more than 213 countries. This is the third highly pathogenic human coronavirus after SARS and MERS-CoV. The coronaviruses have RNA as genetic material and are known to have frequent recombination and mutations in their genome, which lead to the emergence and re-emergence of new virus strains and isolates with novel properties and extended hosts. The genetic mutations and suitable environmental conditions result in the emergence and re-emergence of pathogenic coronaviruses and cause a serious issue to human health and the economy globally. Lectins are the ubiquitous group of proteins that bind to glycosylated molecules. Conclusion: The plant lectins are known to have significant antiviral activities against coronaviruses. Additionally, the plant lectins can be used as potential therapeutics against bacteria, fungus, yeast, and protozoa. In this review, we have discussed the current status of human pathogenic coronavirus emergence and the use of plant lectins as antivirals against SARS-CoV-2.

The presence of multidrug-resistant bacteria in the food chain represents a major public-health concern and has significant economic repercussions. Here we describe the draft genome sequence of serotype O21:H16, multilocus sequence typing (MLST) ST3270 and ribosomal MLST rST120701, multidrug-resistant Escherichia coliCh7_4SIAU, which was isolated from poultry meat collected from a local market in Jeddah, Saudi Arabia.

The Middle East respiratory syndrome (MERS) is a novel lethal zoonotic disease of humans caused by the MERS coronavirus (MERS-CoV). Although MERS is endemic to the Middle East, travelers have exported MERS-CoV on return to their home countries. Clinical manifestations range from mild to severe acute respiratory disease and death. The elderly, immunocompromised, and those with chronic comorbid liver, lung, and hepatic conditions have a high mortality rate. There is no specific treatment. Person-to-person spread causes hospital and household outbreaks, and thus improved compliance with internationally recommended infection control protocols and rapid implementation of infection control measures are required.

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen endemic to the Arabian Peninsula. Dromedary camels are a likely source of infection and the virus probably originated in Africa. We studied the genetic diversity, geographical structure, infection prevalence, and age-associated prevalence among camels at the largest entry port of camels from Africa into the Arabian Peninsula.

Mass gathering events are associated with major public health challenges. The 2014 LancetSeries on the new discipline of mass gatherings medicine was launched at the World Health Assembly of Ministers of Health in Geneva in May, 2014. The Series covered the planning and surveillance systems used to monitor public health risks, public health threats, and experiences of health-care providers from mass gathering events in 2012 and 2013. This follow-up Review focuses on the main public health issues arising from planned mass gathering events held between 2013 and 2018. We highlight public health and research data on transmission of infectious diseases and antibiotic-resistant bacteria, mass casualty incidents, and non-communicable diseases, including thermal disorders. In the events discussed in this Review, the combination of a large influx of people, many from countries with outbreak-prone infectious diseases, with a high degree of crowd interactions imposed substantial burdens on host countries' health systems. The detection and transmission of antibiotic-resistant bacteria in pilgrims attending the Kumbh Mela and the Hajj raise concern of possible globalisation from mass-gathering religious events. Priorities for further investments and opportunities for research into prevention, surveillance, and management of these public health issues are discussed.

Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are examples of emerging zoonotic coronavirus infections capable of person-to-person transmission that result in large-scale epidemics with substantial effects on patient health and socioeconomic factors. Unlike patients with mild illnesses that are caused by other human-pathogenic coronaviruses, patients with SARS or MERS coronavirus infections may develop severe acute respiratory disease with multi-organ failure. The case–fatality rates of SARS and MERS are approximately 10% and 35%, respectively.Both SARS and MERS pose major clinical management challenges because there is no specific antiviral treatment that has been proven to be effective in randomized clinical trials for either infection. Substantial efforts are underway to discover new therapeutic agents for coronavirus infections.Virus-based therapies include monoclonal antibodies and antiviral peptides that target the viral spike glycoprotein, viral enzyme inhibitors, viral nucleic acid synthesis inhibitors and inhibitors of other viral structural and accessory proteins.Host-based therapies include agents that potentiate the interferon response or affect either host signalling pathways involved in viral replication or host factors utilized by coronaviruses for viral replication.The major challenges in the clinical development of novel anti-coronavirus drugs include the limited number of suitable animal models for the evaluation of potential treatments for SARS and MERS, the current absence of new SARS cases, the limited number of MERS cases — which are also predominantly geographically confined to the Middle East — as well as the lack of industrial incentives to develop antivirals for mild infections caused by other, less pathogenic coronaviruses.The continuing threat of MERS-CoV to global health 3 years after its discovery presents a golden opportunity to tackle current obstacles in the development of new anti-coronavirus drugs. A well-organized, multidisciplinary, international collaborative network consisting of clinicians, virologists and drug developers, coupled to political commitment, should be formed to carry out clinical trials using anti-coronavirus drugs that have already been shown to be safe and effective in vitroand/or in animal models, particularly lopinavir–ritonavir, interferon beta-1b and monoclonal antibodies and antiviral peptides targeting the viral spike glycoprotein.

Acinetobacter baumanniihas emerged as a prevalent multidrug-resistant nosocomial pathogen worldwide. Here we report the draft genome sequence of A. baumanniistrain Ab174 isolated from a neonatal patient diagnosed with acute peritonitis.

ABSTRACTMiddle East respiratory syndrome coronavirus (MERS-CoV) is a novel betacoronavirus that has been circulating in the Arabian Peninsula since 2012 and causing severe respiratory infections in humans. While bats were suggested to be involved in human MERS-CoV infections, a direct link between bats and MERS-CoV is uncertain. On the other hand, serological and virological data suggest dromedary camels as the potential animal reservoirs of MERS-CoV. Recently, we isolated MERS-CoV from a camel and its infected owner and provided evidence for the direct transmission of MERS-CoV from the infected camel to the patient. Here, we extend this work and show that identical MERS-CoV RNA fragments were detected in an air sample collected from the same barn that sheltered the infected camel in our previous study. These data indicate that the virus was circulating in this farm concurrently with its detection in the camel and in the patient, which warrants further investigations for the possible airborne transmission of MERS-CoV.IMPORTANCEThis work clearly highlights the importance of continuous surveillance and infection control measures to control the global public threat of MERS-CoV. While current MERS-CoV transmission appears to be limited, we advise minimal contact with camels, especially for immunocompromised individuals, and the use of appropriate health, safety, and infection prevention and control measures when dealing with infected patients. Also, detailed clinical histories of any MERS-CoV cases with epidemiological and laboratory investigations carried out for any animal exposure must be considered to identify any animal source.