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Background and Objectives: Avian respiratory disease complex (RDC) is one of the most detrimental economic diseases that affected different parts of the world. Various pathogens cause the disease, but the most significant viral pathogens include avian influenza virus (AIV), infectious bronchitis virus (IBV), and Newcastle disease virus (NDV) are the most prevalent. To detect these pathogens, various methods have been discovered in the last decades. Detection and characterization of viruses by metagenomics methods have improved our knowledge about the role of virome in the avian complex respiratory disease. Materials and Methods: This research investigates the viral pathogen populations that mostly participate in emerging these diseases using the NGS method RNA-sequencing. In surveillance of ten broiler farms from different cities with respiratory symptoms, trachea samples were collected to determine the pathogenic virome causing the disease. Results: In this metagenomics analysis, nine viral families were identified, comprising 72.82% of RNA viruses, 24.32% of RT viruses, and 2.86% of DNA viruses. RNA viruses had the highest contribution to the respiratory disease complex instead of disease, including paramyxoviridae, orthomyxoviridae, coronaviridae, and picornaviridae viruses. Other viruses from the RNA viruses and DNA virus families were also identified in addition to these results. Conclusion: This research suggests that studies of pathogenic viromes in different diseases can help monitor different diseases and predict their future occurrence.

Anti-inflammatory drugs are in the spotlight of pharmaceutical investigations due to the involvement of this condition in different cancers and diseases. Non-steroidal anti-inflammatory drugs (NSAIDs) are considered to be the most widely used anti-inflammatory drugs. However, the inability of these molecules to distinguish between COX-1 and COX-2 results in concomitant side effects. In the present study, a new algorithmic procedure is applied to build a multi-linear regression model capable of circumventing this problem. In this regard, the structures of FDA-approved NSAIDs and COX-1 and COX-2 molecules were prepared. The top 10 COX-2 specific molecules were selected based on their interaction energies and exploited for similarity searches. The resulting 2000 molecules were subjected to various screening processes. Several dependable bioactivities of these compounds along with partial coefficients of all possible affecting descriptors such as molecular weight, H-acceptor/donor, and polar surface area were calculated. The best multi-linear regression approach was used to analyze the descriptors with the highest impact. Ultimately, a highly reliable model was designed based on 17 screened molecules with higher than 90% anti-inflammatory activity. The attained model was endowed with higher than 84% accuracy according to 5 descriptors, including Log P, Log D, molar refractivity, polarity number, and aromaticity ratio. Our results demonstrated that the bipolarity of drugs is more important than the number of hydrogen bonds to achieve the better anti-inflammatory activity. Moreover, in contrast to prior reports, it is assumable that some Lipinski elements could play a less critical role in drug discovery and improvement efforts. The quantitative structure and activity relationship (QSAR) model formulated in this study demonstrates an accurate prediction of anti-inflammatory activity of NSAID-like structures. Newly suggested structures are highly resembled to third-generation NSAIDs. This property endorses the trustworthiness and reliability of the obtained equation to design a new generation of NSAIDs.

Introduction: Some strains of Escherichia Coli, including intestinal pathogenic strains, commensal strains, and extra intestinal pathogenic E. coli (ExPEC) have a significant impact on human health status. A standard vaccine designed based on conserved epitopes can stimulate a protective immune response against these pathogens. Additionally, enhanced expression at the infection site as a pathogenesis factor in disease is crucial for an ideal vaccine candidate. The IroN protein plays a role in severe infections of E. coli. Hence, this protein will assist in developing the novel and more efficient treatments for E. coli related infections. A better understanding of protein tertiary structure can help to percept their functions and also their interactions with other molecules. There is a growing interest in using bioinformatics tool to make accurate predictions about the functional, immunological, and biochemical features of target antigens. Method: Herein, we aimed to predict the structure of the IroN protein upon its folding and determine their immunological properties. Results: In the present study, using bioinformatics analyses, we identified the highly antigenic regions of IroN protein. Our designed vaccine candidate had the highest immunological properties and folded into a typical beta-barrel structure. Conclusion: The approach of assigning structural and immunological properties of the target antigen to design the vaccine candidate could be deployed as an efficient strategy to circumvent the challenges ahead of empirical methods without dealing with ethical concerns of animal usage and human participants. Although the obtained results are promising, further experimental studies could bring about more insights on the efficiency of the designed vaccine.

The structural consequences of ongoing mutations on the SARS-CoV-2 spike-protein remains to be fully elucidated. These mutations could change the binding affinity between the virus and its target cell. Moreover, obtaining new mutations would also change the therapeutic efficacy of the designed drug candidates. To evaluate these consequences, 3D structure of a mutant spike protein was predicted and checked for stability, cavity sites, and residue depth. The docking analyses were performed between the 3D model of the mutated spike protein and the ACE2 protein and an engineered therapeutic ACE2 against COVID-19. The obtained results revealed that the N501Y substitution has altered the interaction orientation, augmented the number of interface bonds, and increased the affinity against the ACE2. On the other hand, the P681H mutation contributed to the increased cavity size and relatively higher residue depth. The binding affinity between the engineered therapeutic ACE2 and the mutant spike was significantly higher with a distinguished binding orientation. It could be concluded that the mutant spike protein increased the affinity, preserved the location, changed the orientation, and altered the interface amino acids of its interaction with both the ACE2 and its therapeutic engineered version. The obtained results corroborate the more aggressive nature of mutated SARS-CoV-2 due to their higher binding affinity. Moreover, designed ACe2-baased therapeutics would be still highly effective against covid-19, which could be the result of conserved nature of cellular ACE2. Supplementary Information The online version contains supplementary material available at 10.1007/s10989-021-10346-1.

Cancer can be caused by various factors, including the malfunction of tumor suppressor genes and the hyper-activation of proto-oncogenes. Tumor-associated extrachromosomal circular DNA (eccDNA) has been shown to adversely affect human health and accelerate malignant actions. Whole-genome sequencing (WGS) on different cancer types suggested that the amplification of ecDNA has increased the oncogene copy number in various cancers. The unique structure and function of ecDNA, its profound significance in cancer, and its help in the comprehension of current cancer genome maps, renders it as a hotspot to explore the tumor pathogenesis and evolution. Illumination of the basic mechanisms of ecDNA may provide more insights into cancer therapeutics. Despite the recent advances, different features of ecDNA require further elucidation. In the present review, we primarily discussed the characteristics, biogenesis, genesis, and origin of ecDNA and later highlighted its functions in both tumorigenesis and therapeutic resistance of different cancers.

COVID-19 is a rapidly spreading disease, which has caught the world by surprise. Millions of people suffer from illness, and the mortality rates are dramatically high. Currently, there is no specific and immediate treatment for this disease. Remedies are limited to supportive regiments and few antiviral and anti-inflammatory drugs. The lack of a definite cure for COVID-19 is the reason behind its high mortality and global prevalence. COVID-19 can lead to a critical illness with severe respiratory distress and cytokine release. Increased oxidative stress and excessive production of inflammatory cytokines are vital components of severe COVID-19. Micronutrients, metalloids, and vitamins such as iron, manganese, selenium, Zinc, Copper, vitamin A, B family, and C are among the essential and trace elements that play a pivotal role in human nutrition and health. They participate in metabolic processes that lead to energy production. In addition, they support immune functions and act as antioxidants. Therefore, maintaining an optimal level of micronutrients intake, particularly those with antioxidant activities, is essential to fight against oxidative stress, modulate inflammation, and boost the immune system. Therefore, these factors could play a crucial role in COVID-19 prevention and treatment. In this review, we aimed to summarize antiviral properties of different vitamins and minerals. Moreover, we will investigate the correlation between them and their effects in COVID-19 patients.

AIM: The present study implemented an RT-qPCR assay for the detection and quantification of human cosavirus in stool specimens from pediatric patients involved in acute gastroenteritis. BACKGROUND: Human cosavirus is a newly recognized virus that seems to be partly related to acute gastroenteritis in pediatric patients. However, the relationship between human cosavirus and diseases in humans is unclear METHODS: From January 2018 to December 2019, a total of 160 stool samples were collected from pediatric patients presenting with acute gastroenteritis in a hospital in Karaj, Iran. After viral RNA extraction, RT-qPCR was performed to amplify the 5’UTR region of the human cosavirus genome and viral load was analyzed. RESULTS: The human cosavirus genomic RNA was detected in 4/160 (2.5%) stool samples tested. The maximum viral load was determined to be 4.6×10(6) copies/ml in one sample obtained from a 4-year-old patient. CONCLUSION: The human cosavirus as a new member of the Picornaviridae family was illustrated in fecal samples from pediatric patients with acute gastroenteritis in Iran. This is the first documentation of human cosavirus circulation in Iranian children.

Infections with HCV, HBV and poliovirus are still considered to be substantial global health burdens. Vaccination is one of the most important preventive strategies against these infections. Multi-epitope vaccines are presented as novel strategies to circumvent the limitations associated with conventional vaccines. Given these circumstances, a multi-epitope protein was designed using the predicted high score epitopes of the antigens from HCV, HBV and Poliovirus. To this end, the sequences of HCV core protein, HBV small surface antigen and VPs of Poliovirus were collected and the consensus sequence of these antigens were obtained using BLAST and MSA analyses. Then, the physicochemical properties of these antigens along with their high score B and T-cell epitopes were predicted using various softwares. The obtained epitopes were connected with proper linkers to build the final 500 amino acids HHP protein. The secondary and tertiary structure of the HHP as well as its physicochemical properties and immunological properties were predicted using different tools. Assessment of various properties of the designed protein indicated that the HHP poly-epitope is an immunogenic and non-allergen antigen, which can derive humoral and cellular immune responses against HCV, HBV and Poliovirus infections.

Atherosclerosis is a complex disease related to cardiovascular disorders and is one of the most considerable causes of mortality worldwide. It has been shown that the immune system plays a pivotal role in generating atherosclerosis plaques. The atherosclerosis plaques form via activation of endothelial cells by recruiting adhesion molecules such as VCAM1. Therefore, VCAM1 could be considered as a suitable target to design immune-therapeutics. In this regard, we have lunched an in silico approach to design an immunotoxin against VCAM1. The structure of an anti-VCAM1 antibody was predicted using homology modeling software. The structure of the predicted chains were linked by (Gly4Ser)3 linker. Then, using various modeling software the structure of the GrB was linked to the antibody structure via an adaptor sequence. The final structure was energy minimized, evaluated for accuracy and characterized for its biological properties. Our results indicated that the employed structure prediction method has successfully managed to model the immunotoxin structure. Moreover, our results indicated that the designed immunotoxin is capable of VCAM1 interaction with proper orientation involving its C–D loop. In conclusion it should be pointed out that, the employed in silico approach could pave the way for precise and accurate design of immune-therapeutic agents against cancer. Using this approach we have designed an immunotoxin capable of VCAM1 targeting in a proper orientation and following cancer cell destruction by the toxin domain of the molecule.

Introduction: Vaccine studies against Pseudomonas aeruginosa have often focused on outer membrane proteins (OPRs) due to their potent stimulation of the immune response. Using major outer membrane proteins of cell walls (mOMPs) of P. aeruginosa and other Gram-negative bacteria actively stimulate the immune system without any toxic side effects. Moreover, these antigens show immunological cross-reactivity with mOMPs of other serotypes belonging to the same species. The main OPRs of P. aeruginosa, OprF, and OprL, have received much attention from biologists as the potential OPR-based vaccine candidates. Methods: Homology modeling of OprF and OprL was done based on the template structures obtained from the BLAST search. The quality of OprF and OprL molecules was assessed using GMQE and QMEAN4 quality assessment tools. The secondary structure of the proteins was predicted as well as the structural topology, subcellular localization, functional analyses, signal peptide and B cell epitopes of proteins. Results: The structures of OprF and OprL proteins were successfully modeled and assessed using 4RLC-A and 4G4V-A as template structures. The regions of the proteins with a high B cell epitope density were identified as candidates for vaccine design. These regions contain functional and exposed amino acids. In these regions, the majority of amino acids were hydrophilic, flexible and accessible. Conclusion: It should be noted that in silico approaches are appealing alternatives for empirical methods. These approaches could pave the way for precise vaccine design efforts with lower cost and time.

Epsilon toxin of the Clostridium perfringens garnered a lot of attention due to its potential for toxicity in humans, extreme potency for cytotoxicity in mice and lack of any approved therapeutics prescribed for human. However, the intricacies of the Epsilon toxin action mechanism are yet to be understood. In this regard, various in silico tools have been exploited to model and refine the 3D structure of the toxin and its two receptors. The receptor proteins were embedded into designed lipid membranes within an aqueous and ionized environment. Thereafter, the modeled structures subjected to series of consecutive molecular dynamics runs to achieve the most natural like coordination for each model. Ultimately, protein-protein interaction analyses were performed to understand the probable action mechanism. The obtained results successfully confirmed the accuracy of employed methods to achieve high quality models for the toxin and its receptors within their lipid bilayers. Molecular dynamics analyses lead the structures to a more native like coordination. Moreover, the results of previous empirical studies were confirmed, while new insights for action mechanisms including the detailed roles of Hepatitis A virus cellular receptor 1 (HAVCR1) and Myelin and lymphocyte protein (MAL) proteins were achieved. In light of previous and our observations, we suggested novel models which elucidated the existing interplay between potential players of Epsilon toxin action mechanism with detailed structural evidences. These models would pave the way to have more robust understanding of the Epsilon toxin biology, more precise vaccine construction and more successful drug (inhibitor) design.

Background: Conventionalmethods of detecting Brucella spp. suffer from technical and biological complications. Besides, newly characterized species of the genus Brucella could be neglected by previously designed polymerase chain reaction (PCR) tests. Therefore, a more accurate PCR-based test seems to be imminently needed. Materials and methods: Blood samples were collected from 39 patients diagnosed with brucellosis and 25 healthy controls. Multiple sequence alignments (MSA) were performed on 500 Omp2-related protein and gene sequences. Thereafter, specific primers were designed and synthesized for the regions with highest conservancy. The collected samples were assessed by PCR test. To overcome the cross-reactivity issue, PCR thermal program was optimized regarding annealing time and temperature.Results: The MSA results indicated that the N terminus region of the Omp2 protein (DNA 5' end) is associated with highest conservancy. Primers with highest specificity were designed and synthesized. A two-step PCR reaction was successfully designed and optimized. The desirable bands were observed in clinical samples with high accuracy. Conclusion: It should be pointed out that using a precisely designed primer pair would bring about early infection detection, more success to detect all natural variants and higher cost-to-efficacy ratio in comparison to other detection methods.

Coeliac disease (CD) is a chronic autoimmune disease that is characterized by malabsorption in sensitive individuals. CD is triggered by the ingestion of grains containing gluten. CD is concomitant with several other disorders, including dermatitis herpetiformis, selective IgA deficiency, thyroid disorders, diabetes mellitus, various connective tissue disorders, inflammatory bowel disease, and rheumatoid arthritis. The advent of high throughput technologies has provided a massive wealth of data which are processed in various omics scale fields. These approaches have revolutionized the medical research and monitoring of the biological systems. In this regard, omics scaled analyses of CD by Comparative Toxicogenomics Database (CTD), DISEASES, and GeneCards databases have retrieved 2656 CD associated genes. Amongst, 54 genes were assigned by Venn Diagram of the intersection to be shared by these 3 databases for CD. These common genes were subjected to further analysis and screening. The Enrich database, GeneMANIA, Cytoscape, and WebGestalt (WEB-based GEne SeT AnaLysis Toolkit) were employed for functional analysis. These analyses indicated that the obtained genes are mainly involved in the immune system and signalling pathways related to autoimmune diseases. The STAT1, ALB, IL10, IL2, IL4, IL17A, TGFB1, IL1B, IL6, TNF, IFNG hub genes were particularly indicated to have significant roles in CD. Functional analyses of these hub genes by GeneMANIA indicated that they are involved in immune systems regulation. Moreover, 25 out of 54 genes were identified to be seed genes by the WebGestalt database. Gene set analysis with GEO2R tool from Gene Expression Omnibus (GEO) showed that there were 15 significant genes in GSE76168, 29 significant genes in GSE87460, 12 significant genes in GSE87458, 9 significant genes in GSE87457, 3753 significant genes in GSE112102 and 1043 significant genes in GSE102991 with differential expression in coeliac patients compared to controls. The IRF1and STAT1 genes were common between the significant genes from GEO and the 54 CD related genes from three public databases. In the light these results, nine key genes, including IRF1, STAT1, IL17A, TGFB1, ALB, IL10, IL2, IL4, and IL1B, were identified to be associated with CD. These findings could be used to find novel diagnostic biomarkers, understand the pathology of disease, and devise more efficient treatments.

CD37 is a member of tetra-spanning superfamily (characterized by their four transmembrane domains). It is one of the specific proteins for normal and malignant mature B cells. Anti CD37 monoclonal antibodies are reported to improve the overall survival in CLL. These therapeutics will increase the efficacy and reduce the toxicity in patients with both newly diagnosed and relapsed and refractory disease. Recent clinical trials have shown promising outcomes for these agents, administered both as monotherapy and in combination with standard chemotherapeutics. Long-term follow-up of combination regimens has even raised the question of whether the patients with CLL could be treated with intensive chemo-immunotherapy. In the present study, CD37 is introduced as an appealing target to treat B cell malignancies. The anti-CD37 antibodies as one of the most successful therapeutics against CD37 are introduced and the clinical outcomes of their exploitation are explained.

Beak and feather disease virus (BFDV) is a common avian circovirus infection of wild Psittaciformes and is a recognised threat to endangered psittacine species. Currently, there is a requirement to develop BFDV antigen for diagnostic purposes and since efforts to propagate BFDV in vitro have so far been unsuccessful the entire coding region of BFDV ORF C1 was expressed in Sf9 insect cells using a baculovirus expression system. The entire coding region of BFDV ORF C1, the presumptive capsid, was expressed in Sf9 insect cells using baculovirus expression system. Electron microscopic examination of negatively stained material demonstrated that the recombinant protein self-assembled to produce virus-like particles (VLPs) thus confirming that ORF C1 is likely to be the sole determinant for capsid construction in vivo. BFDV VLPs also possessed haemagglutinating activity which provides further evidence that self-assembled BFDV VLPs retain receptor mediated biological activity and that the determinants for BFDV haemagglutination activity rely solely on the capsid protein. The recombinant protein reacted with anti-BFDV sera from naturally immune parrots and cockatoo and from chickens experimentally inoculated with native BFDV in both Western blots and haemagglutination inhibition (HI) assay. BFDV VLPs were also a suitable replacement antigen for serological detection of BFDV antibody by HI.

Psittacine beak and feather disease (PBFD) is recognized as a threat for endangered psittacine birds in Australia, New Zealand and South Africa. Several diagnostic methods for the detection of beak and feather disease virus (BFDV) infection have been developed but there are few studies comparing the relative merits or sensitivity and specificity of each diagnostic test. In this report, the results of PCR, haemagglutination (HA) and haemagglutination inhibition (HI) testing of diagnostic samples collected from 679 samples from a range of psittacine bird species suspected of being infected with BFDV are summarized and compared. There was a strong agreement (kappa = 0·757; P1 : 40 960) and four false-positive PCR results were detected in a batch of four feather samples. Of 143 birds that were feather PCR positive, only two had detectable HI antibody, and these birds were also feather HA negative, suggesting that they were developing immunity to recent infection. All birds with HI antibody were negative on feather HA testing. The assays confirmed BFDV infection in two endangered swift parrots (Lathamus discolor) and phylogenetic analysis of the sequence data generated from ORF V1 of these isolates provide further evidence of BFDV genotypes clustering in parallel with the Loriidae, Cacatuidae and Psittacidae.