Genetic determinants of SARS-CoV-2 and the clinical outcome of COVID-19 in Southern Bangladesh.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a severe impact on population health. The genetic determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in southern Bangladesh are not well understood. METHODS: This study aimed to determine the genomic variation in SARS-CoV-2 genomes that have evolved over 2 years of the pandemic in southern Bangladesh and their association with disease outcomes and virulence of this virus. We investigated demographic variables, disease outcomes of COVID-19 patients and genomic features of SARS-CoV-2. RESULTS: We observed that the disease severity was significantly higher in adults (85.3%) than in children (14.7%), because the expression of angiotensin-converting enzyme-2 (ACE-2) diminishes with ageing that causes differences in innate and adaptive immunity. The clade GK (n = 66) was remarkable between June 2021 and January 2022. Because of the mutation burden, another clade, GRA started a newly separated clustering in December 2021. The burden was significantly higher in GRA (1.5-fold) highlighted in mild symptoms of COVID-19 patients than in other clades (GH, GK, and GR). Mutations were accumulated mainly in S (22.15 mutations per segment) and ORF1ab segments. Missense (67.5%) and synonymous (18.31%) mutations were highly noticed in adult patients with mild cases rather than severe cases, especially in ORF1ab segments. Moreover, we observed many unique mutations in S protein in mild cases compared to severe, and homology modeling revealed that those might cause more folding in the protein's alpha helix and beta sheets. CONCLUSION: Our study identifies some risk factors such as age comorbidities (diabetes, hypertension, and renal disease) that are associated with severe COVID-19, providing valuable insight regarding prioritizing vaccination for high-risk individuals and allocating health care and resources. The findings of this work outlined the knowledge and mutational basis of SARS-CoV-2 for the next treatment steps. Further studies are needed to confirm the effects of structural and functional proteins of SARS-CoV-2 in detail for monitoring the emergence of new variants in future.

Characteristics, management and outcomes of critically ill COVID-19 patients admitted to ICU in hospitals in Bangladesh: a retrospective study.

OBJECTIVES: This study aimed to analyze the epidemiological and clinical characteristics of COVID-19 cases and investigate risk factors including comorbidities and age in relation with the clinical aftermath of COVID-19 in ICU admitted cases in Bangladesh. METHODS: In this retrospective study, epidemiological and clinical characteristics, complications, laboratory results, and clinical management of the patients were studied from data obtained from 168 individuals diagnosed with an advanced prognosis of COVID-19 admitted in two hospitals in Bangladesh. RESULTS: Individuals in the study sample contracted COVID-19 through community transmission. 56.5% (n = 95) cases died in intensive care units (ICU) during the study period. The median age was 56 years and 79.2% (n = 134) were male. Typical clinical manifestation included Acute respiratory distress syndrome (ARDS) related complications (79.2%), fever (54.2%) and cough (25.6%) while diabetes mellitus (52.4%), hypertension (41.1%) and heart diseases (16.7%) were the conventional comorbidities. Clinical outcomes were detrimental due to comorbidities rather than age and comorbid individuals over 50 were at more risk. In the sample, oxygen saturation was low (< 95% SpO2) in 135 patients (80.4%) and 158 (93.4%) patients received supplemental oxygen. Identical biochemical parameters were found in both deceased and surviving cases. Administration of antiviral drug Remdesivir and the glucocorticoid, Dexamethasone increased the proportion of surviving patients slightly. CONCLUSIONS: Susceptibility to developing critical illness due to COVID-19 was found more in comorbid males. These atypical patients require more clinical attention from the prospect of controlling mortality rate in Bangladesh.

Epitope-based universal vaccine for Human T-lymphotropic virus-1 (HTLV-1).

Human T-cell leukemia virus type 1 (HTLV-1) was the first oncogenic human retrovirus identified in humans which infects at least 10-15 million people worldwide. Large HTLV-1 endemic areas exist in Southern Japan, the Caribbean, Central and South America, the Middle East, Melanesia, and equatorial regions of Africa. HTLV-1 TAX viral protein is thought to play a critical role in HTLV-1 associated diseases. We have used numerous bio-informatics and immuno-informatics implements comprising sequence and construction tools for the construction of a 3D model and epitope prediction for HTLV-1 Tax viral protein. The conformational linear B-cell and T-cell epitopes for HTLV-1 TAX viral protein have been predicted for their possible collective use as vaccine candidates. Based on in silico investigation two B cell epitopes, KEADDNDHEPQISPGGLEPPSEKHFR and DGTPMISGPCPKDGQPS spanning from 324-349 and 252-268 respectively; and T cell epitopes, LLFGYPVYV, ITWPLLPHV and GLLPFHSTL ranging from 11-19, 163-171 and 233-241 were found most antigenic and immunogenic epitopes. Among different vaccine constructs generated by different combinations of these epitopes our predicted vaccine construct was found to be most antigenic with a score of 0.57. T cell epitopes interacted strongly with HLA-A*0201 suggesting a significant immune response evoked by these epitopes. Molecular docking study also showed a high binding affinity of the vaccine construct for TLR4. The study was carried out to predict antigenic determinants of the Tax protein along with the 3D protein modeling. The study revealed a potential multi epitope vaccine that can raise the desired immune response against HTLV-1 and be useful in developing effective vaccines against Human T-lymphotropic virus.

Molecular docking and dynamics study of natural compound for potential inhibition of main protease of SARS-CoV-2.

Newly emerged SARS-CoV-2 made recent pandemic situations across the globe is accountable for countless unwanted death and insufferable panic associated with co-morbidities among mass people. The scarcity of appropriate medical treatment and no effective vaccine or medicine against SARS-CoV-2 has turned the situation worst. Therefore, in this study, we made a deep literature review to enlist plant-derived natural compounds and considered their binding mechanism with the main protease of SARS-CoV-2 through combinatorial bioinformatics approaches. Among all, a total of 14 compounds were filtered where Carinol, Albanin, Myricetin were had better binding profile than the rest of the compounds with having binding energy of -8.476, -8.036, -8.439 kcal/mol, respectively. Furthermore, MM-GBSA calculations were also considered in this selection process to support docking studies. Besides, 100 ns molecular dynamics simulation endorsed the rigid nature, less conformational variation and binding stiffness. As this study, represents a perfect model for SARS-CoV-2 main protease inhibition through bioinformatics study, these potential drug candidates may assist the researchers to find a superior and effective solution against COVID-19 after future experiments.Communicated by Ramaswamy Sarma.