Differential gene expression profiling reveals potential biomarkers and pharmacological compounds against SARS-CoV-2: insights from machine learning and bioinformatics approaches (preprint)

The precise role of severe acute respiratory syndrome coronavirus 2 in the pathophysiology of the nasopharyngeal tract (NT) is still unfathomable. Therefore, we used the machine learning methods to analyze 22 RNAseq datasets from COVID 19 patients (n=8), recovered individuals (n=7), and healthy individuals (n=7) to find disease-related differentially expressed genes (DEGs). In comparison to healthy controls, we found 1960 and 153 DEG signatures in COVID 19 patients and recovered individuals, respectively. We compared dysregulated DEGs to detect critical pathways and gene ontology (GO) connected to COVID 19 comorbidities. In COVID-19 patients, the DEG miRNA and DEG transcription factors (TFs) interactions network analysis revealed that E2F1, MAX, EGR1, YY1, and SRF were the most highly expressed TFs, whereas hsa-miR-19b, hsa-miR-495, hsa miR 340, hsa miR 101, and hsa-miR-19a were the overexpressed miRNAs. Three chemical agents (Valproic Acid, Alfatoxin B1, and Cyclosporine) were abundant in COVID 19 patients and recovered individuals. Mental retardation, mental deficit, intellectual disability, muscle hypotonia, micrognathism, and cleft palate were the significant diseases associated with COVID-19 by sharing DEGs. Finally, we detected DEGs impacted by severe acute respiratory syndrome coronavirus 2 infection and mediated by TFs and miRNA expression, indicating that severe acute respiratory syndrome coronavirus 2 infection may contribute to various comorbidities. These pathogenetic findings can provide some crucial insights into the complex interplay between COVID 19 and the recovery stage and support its importance in the therapeutic development strategy to combat against COVID 19 pandemic.

Insights from a computational analysis of the SARS-CoV-2 Omicron variant: Host-pathogen interaction, pathogenicity and possible therapeutics (preprint)

Prominently accountable for the upsurge of COVID-19 cases as the world attempts to recover from the previous two waves, Omicron has further threatened the conventional therapeutic approaches. Omicron is the fifth variant of concern (VOC), which comprises more than 10 mutations in the receptor-binding domain (RBD) of the spike protein. However, the lack of extensive research regarding Omicron has raised the need to establish correlations to understand this variant by structural comparisons. Here, we evaluate, correlate, and compare its genomic sequences through an immunoinformatic approach with wild and mutant RBD forms of the spike protein to understand its epidemiological characteristics and responses towards existing drugs for better patient management. Our computational analyses provided insights into infectious and pathogenic trails of the Omicron variant. In addition, while the analysis represented South Africa's Omicron variant being similar to the highly-infectious B.1.620 variant, mutations within the prominent proteins are hypothesized to alter its pathogenicity. Moreover, docking evaluations revealed significant differences in binding affinity with human receptors, ACE2 and NRP1. Owing to its characteristics of rendering existing treatments ineffective, we evaluated the drug efficacy against their target protein encoded in the Omicron through molecular docking approach. Most of the tested drugs were proven to be effective. Nirmatrelvir (Paxlovid), MPro 13b, and Lopinavir displayed increased effectiveness and efficacy, while Ivermectin showed the best result against Omicron.

The First Wave of COVID-19 Pandemic: Experiences from Bangladesh (preprint)

The ongoing pandemic COVID-19 is caused by Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2), has wreaked havoc globally by affecting millions of lives. Although different countries found the implementation of emergency measures useful to combat the viral pandemic (first wave), many countries are now experiencing the resurgence of COVID-19 even after following strict containment guidelines (second wave). Country-specific lessons learned from the first wave of infection appeared to be useful in the successful battle of possible second wave outbreak. In this article, we examined the situation in Bangladesh during the first wave COVID-19 outbreak and discussed the demographic, political, economic, social and environmental influences on the mitigation strategies employed by the country to combat the pandemic. We also tried to explore the preparedness and precautionary measures taken by responsible authorities, choice of strategies implemented and effectiveness of response from government and relevant agencies. Finally, we discussed the possible strategies that might help Bangladesh survive a second wave outbreak based on the experiences from the first wave of the ongoing pandemic.

Choice of assemblers has a critical impact on de novo assembly of SARS-CoV-2 genome and characterizing variants (preprint)

BackgroundCoronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic following its initial emergence in China. Using next-generation sequencing technologies, a large number of SARS-CoV-2 genomes are being sequenced at an unprecedented rate and being deposited in public repositories. For the de novo assembly of the SARS-CoV-2 genomes, a myriad of assemblers is being used, although their impact on the assembly quality has not been characterized for this virus. In this study, we aim to understand the variabilities on assembly qualities due to the choice of the assemblers. ResultsWe performed 6,648 de novo assemblies of 416 SARS-CoV-2 samples using 8 different assemblers with different k-mers. We used Illumina paired-end sequencing reads and compared the genome assembly quality to that of different assemblers. We showed the choice of assemblers plays a significant role in reconstructing the SARS-CoV-2 genome. Two metagenomic assemblers e.g. MEGAHIT and metaSPAdes performed better compared to others in most of the assembly quality metrics including, recovery of a larger fraction of the genome, constructing larger contigs and higher N50, NA50 values etc. We showed that at least 09% (259/2,873) of the variants present in the assemblies between MEGAHIT and metaSPAdes are unique to the assembly methods. ConclusionOur analyses indicate the critical role of assembly methods for assembling SARS-CoV-2 genome using short reads and their impact on variant characterization. This study could help guide future studies to determine which assembler is best suited for the de novo assembly of virus genomes.

Engineering Novel Epitope-Based Subunit Vaccine against SARS-CoV-2 by Exploring the Immunoinformatics Approach (preprint)

As the number of infections and deaths caused by the recent COVID-19 pandemic is increasing dramatically day-by-day, scientists are rushing towards developing possible counter-measures to fight the deadly virus, SARS-CoV-2. Although many efforts have already been put forward for designing and developing potential vaccines, however, most of them are proved to possess negative consequences. Therefore, in this study, the methods of immunoinformatics were exploited to design novel epitope-based subunit vaccine against the SARS-CoV-2, targeting four essential proteins of the virus i.e., spike glycoprotein, nucleocapsid phosphoprotein, membrane glycoprotein, and envelope protein. The highly antigenic, non-allergenic, non-toxic, non-human homolog and 100% conserved (across other isolates from different regions of the world) epitopes were used for constructing the vaccine. In total, fourteen CTL epitopes and eighteen HTL epitopes were used to construct the vaccine. Thereafter, several in silico validations i.e., the molecular docking, molecular dynamics simulation (including the RMSF and RMSD studies), and immune simulation studies were also performed which predicted that the designed vaccine should be quite safe, effective, and stable within the biological environment. Finally, in silico cloning and codon adaptation studies were also conducted to design an effective mass production strategy of the vaccine. However, more in vivo and in vitro studies are required on the predicted vaccine to finally validate its safety and efficacy.

COVID-19 Pandemic Burden on Global Economy: A Paradigm Shift (preprint)

The pandemic caused by SARS-CoV-2 virus obstructed the Chinese economy and has expanded to the rest of the world at a rapid pace affecting at least 215 countries, areas and territories. The advancement of the disease and its economic repercussions is profoundly ambiguous, making it challenging for policymakers to formulate suitable microeconomic and macroeconomic policy responses. The scenarios in this paper illustrate how an outbreak could significantly affect the global economy in the short run. It has been estimated that each additional month of crisis would cost from about 2.5-3% of the global GDP and that the GDP growth would take a blow, reaching about 3-6%, depending on the country. Scenarios also suggest that GDP can drop by more than 10% and even exceed 15% in some countries. Via addressing the economic consequence of COVID-19 in different industries and countries, the paper presents assessments of the likely global economic costs of COVID-19 and the GDP growth of different countries. Economies will be negatively affected because of the high number of jobs at risk. Countries highly dependent on foreign trade are more negatively affected. Given that disease and its economic influence are highly unpredictable in numerous aspects, the global economy at the moment is the most critically threatened in history.

Combating COVID-19 Pandemic in Bangladesh: A Memorandum from Developing Country (preprint)

This paper is purposed to delineate the current situation around Bangladesh as well as impacts of Coronavirus Disease-2019 (COVID-19) around the country and how the people over here are encountering this threatening pandemic. COVID-19 is an international epidemic that has got rapid wide-spread throughout different countries of the world to date. After its first outbreak in China different continents started to make sense and get aware against COVID-19 though, due to its special strategy of transmission several countries have been quite deteriorated preventing it. All the countries are moving at their best forward to find out any solution so that whole world could get rid of this horrifying situation as soon as possible. The authors here have reported an overview of how the outbreak of COVID-19 had put its commence in Bangladesh and to date how people over here have been tracing the way to tackle this havoc. Also, the changes that have brought around due to the crisis have offered us some fertile lessons that are enunciated here by the authors. To conclude, special considerations are anticipated to be highlighted pertaining COVID-19 outbreak in Bangladesh.

Pathogenesis, Diagnosis and Possible Therapeutic Options for COVID-19 (preprint)

The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread so rapidly and severely affected the people of almost every country in the world. The highly contagious nature of this virus makes it difficult to take control of the present pandemic situation. With no specific treatment available, the coronavirus disease 2019 (COVID-19) presents a threat to people of all ages including the elderly people and people with other medical complications as a vulnerable group to this disease. Better understanding of viral pathogenesis, appropriate preventive measures, early diagnosis and supportive treatments of the infected patients are now the general solutions to fight against this viral transmission. But, as an emerging disease, most about it remains still poorly understood. This article holds an overview on the origin and structure, pathogenesis, diagnosis and possible therapeutic options for the causative agent, SARS-CoV-2 and disease, COVID-19. However, few therapeutic options, laboratory experiments and other strategies proposed here need to be further clinically tested.

The Essential Facts of Wuhan Novel Coronavirus Outbreak in China and Epitope-based Vaccine Designing against 2019-nCoV (preprint)

Wuhan Novel Coronavirus disease (COVID-19) outbreak has become a global outbreak which has raised the concern of scientific community to design and discover a definitive cure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading. To date, no antiviral therapy or vaccine is available which can effectively combat the infection caused by this virus. This study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against SARS-CoV-2. Later, molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. Hopefully, this study will contribute to uphold the present efforts of the researches to secure a definitive treatment against this lethal virus.