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Background: Frontonasal dysplasia type-2(FND2), a rare phenotypically variable and heterogeneous developmental anomaly resulting from mutation of the ALX4 gene, is primarily characterized by malformation of the skull and facial skeleton. This study was designed to showcase a clinical, imaging, and genetic analysis of FND2 in a consanguineous family of Bangladeshi origin. Methodology: Clinical imaging and whole genome sequencing of mother, father and patient was done by using Nextera DNA flex library preparation kit (Illumina, USA) using Novaseq 6000 next generation sequencer to find out ALX4 mutation which causes FND2 in patient. Result: We report the clinical as well as molecular findings in an 8-year-old girl with FND2. The child presented with various characteristic features of skull and facial anomalies associated with FND 2 along with numerous other features many of which have not been described in previous literature. The parents also showed some key clinical, radiological, and genetic features of FND 2. The whole genome sequencing (WGS) revealed homozygosity for a 793C-T transition in the ALX4 gene, which resulted in premature termination at codon 265 (p.Arg265Ter). Both of her parents were heterozygous carriers of ALX4 mutation. Conclusions: This is the first report that associates clinical, imaging, and genomics analyses in a Bangladeshi patient for better understanding the disease FND2. These results will facilitate diagnosis and genetic counseling of the future FND2 patients.

Abstract Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID -19, is constantly evolving, requiring continuous genomic surveillance. In this study, we used whole-genome sequencing to investigate the genetic epidemiology of SARS-CoV-2 in Bangladesh, with particular emphasis on identifying dominant variants and associated mutations. We used high-throughput next-generation sequencing (NGS) to obtain DNA sequences from COVID-19 patient samples and compared these sequences to the Wuhan SARS-CoV-2 reference genome using the Global Initiative for Sharing All Influenza Data (GISAID). Our phylogenetic and mutational analyzes revealed that the majority (88%) of the samples belonged to the pangolin lineage B.1.1.25, whereas the remaining 11% were assigned to the parental lineage B.1.1. Two main mutations, D614G and P681R, were identified in the spike protein sequences of the samples. The D614G mutation, which is the most common, decreases S1 domain flexibility, whereas the P681R mutation may increase the severity of viral infections by increasing the binding affinity between the spike protein and the ACE2 receptor. We employed molecular modeling techniques, including protein modeling, molecular docking, and quantum mechanics/molecular mechanics (QM/MM) geometry optimization, to build and validate three-dimensional models of the S_D614G-ACE2 and S_P681R-ACE2 complexes from the predominant strains. The description of the binding mode and intermolecular contacts of the referenced systems suggests that the P681R mutation may be associated with increased viral pathogenicity in Bangladeshi patients due to enhanced electrostatic interactions between the mutant spike protein and the human ACE2 receptor, underscoring the importance of continuous genomic surveillance in the fight against COVID -19. Finally, the binding profile of the S_D614G-ACE2 and S_P681R-ACE2 complexes offer valuable insights to deeply understand the binding site characteristics that could help to develop antiviral therapeutics that inhibit protein–protein interactions between SARS-CoV-2 spike protein and human ACE2 receptor.

Abstract The impact of SARS-CoV-2 infection on the nasopharyngeal microbiome has not been well characterised. We sequenced genetic material extracted from nasopharyngeal swabs of SARS-CoV-2-positive individuals who were asymptomatic (n = 14), had mild (n = 64) or severe symptoms (n = 11), as well as from SARS-CoV-2-negative individuals who had never-been infected (n = 5) or had recovered from infection (n = 7). Using robust filters, we identified 1345 taxa with approximately 0.1% or greater read abundance. Overall, the severe cohort microbiome was least diverse. Bacterial pathogens were found in all cohorts, but fungal species identifications were rare. Few taxa were common between cohorts suggesting a limited human nasopharynx core microbiome. Genes encoding resistance mechanisms to 10 antimicrobial classes (> 25% sequence coverages, 315 genes, 63 non-redundant) were identified, with β-lactam resistance genes near ubiquitous. Patients infected with SARS-CoV-2 (asymptomatic and mild) had a greater incidence of antibiotic resistance genes and a greater microbial burden than the SARS-CoV-2-negative individuals. This should be considered when deciding how to treat COVID-19 related bacterial infections.

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic which has brought a great challenge to public health. After the first emergence of novel coronavirus SARS-CoV-2 in the city of Wuhan, China, in December 2019. As of March 2020, SARS-CoV-2 was first reported in Bangladesh and since then the country has experienced a steady rise in infections, resulting in 13,355,191 cases and 29,024 deaths as of 27 February 2022. Bioinformatics techniques are used to predict B cell and T cell epitopes from the new SARS-CoV-2 spike glycoprotein in order to build a unique multiple epitope vaccine. The immunogenicity, antigenicity scores, and toxicity of these epitopes were evaluated and chosen based on their capacity to elicit an immune response. Result The best multi-epitope of the possible immunogenic property was created by combining epitopes. EAAAK, AAY, and GPGPG linkers were used to connect the epitopes. In several computer-based immune response analyses, this vaccine design was found to be efficient, as well as having high population coverage. Conclusion This research is entirely reliant on the development of epitope-based vaccines, and these in silico findings would represent a major step forward in the development of a vaccine that might eradicate SARS-CoV-2 in Bangladeshi patients.

Abstract The microbiota of the nasopharyngeal tract (NT) play a role in host immunity against respiratory infectious diseases. However, scant information is available on interactions of SARS-CoV-2 with the nasopharyngeal microbiome. This study characterizes the effects of SARS-CoV-2 infection on human nasopharyngeal microbiomes and their relevant metabolic functions. Twenty-two (n = 22) nasopharyngeal swab samples (including COVID-19 patients = 8, recovered humans = 7, and healthy people = 7) were collected, and underwent to RNAseq-based metagenomic investigation. Our RNAseq data mapped to 2281 bacterial species (including 1477, 919 and 676 in healthy, COVID-19 and recovered metagenomes, respectively) indicating a distinct microbiome dysbiosis. The COVID-19 and recovered samples included 67% and 77% opportunistic bacterial species, respectively compared to healthy controls. Notably, 79% commensal bacterial species found in healthy controls were not detected in COVID-19 and recovered people. Similar dysbiosis was also found in viral and archaeal fraction of the nasopharyngeal microbiomes. We also detected several altered metabolic pathways and functional genes in the progression and pathophysiology of COVID-19. The nasopharyngeal microbiome dysbiosis and their genomic features determined by our RNAseq analyses shed light on early interactions of SARS-CoV-2 with the nasopharyngeal resident microbiota that might be helpful for developing microbiome-based diagnostics and therapeutics for this novel pandemic disease.

Abstract Objective The major objective of the study was to sequence the whole genome of four Bangladeshi individuals and identify variants that are known to be associated with functional changes or disease states. We also carried out an ontology analysis to identify the functions and pathways most likely to be affected by these variants. Results We identified around 900,000 common variants and close to 5 million unique ones in all four of the individuals. This included over 11,500 variants that caused nonsynonymous changes in proteins. Heart function associated pathways were heavily implicated by the ontology analysis; corroborating previous studies that claimed the Bangladeshi population as highly susceptible to heart disorders. Two variants were found that have been previously identified as pathogenic factors in familial hypercholesteremia and structural disorders of the heart. Other pathogenic variants we found were associated with pseudoxanthoma elasticum, cancer progression, polyagglutinable erythrocyte syndrome, preeclampsia, and others.