Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), is rapidly acquiring new mutations. Analysis of these mutations is necessary for gaining knowledge regarding different aspects of therapeutic development. Previously, we have reported a Sanger method-based genome sequence of a viral isolate named SARS-CoV-2 NIB-1, circulating in Bangladesh. The genome has four novel non-synonymous mutations in V121D, V843F, A889V, and G1691C positions. Results Using different computational tools, we have found V121D substitution has the potential to destabilize the non-structural protein-1 (NSP-1). NSP-1 inactivates the type-1 interferon-induced antiviral system. Hence, this mutant could be a basis of attenuated vaccines against SARS-CoV-2. V843F, A889V, and G1691C are all located in nonstructural protein-3 (NSP-3). G1691C can decrease the flexibility of the protein. V843F and A889V might change the binding pattern and efficacy of SARS-CoV-2 papain-like protease (PLPro) inhibitor GRL0617. V843F substitution in PLPro was the most prevalent mutation in the clinical samples. This mutation showed a reduced affinity for interferon-stimulated gene-15 protein (ISG-15) and might have an impact on innate immunity and viral spread. However, V843F+A889V double mutant exhibited the same binding affinity as wild type PLPro. A possible reason behind this phenomenon can be that V843F is a conserved residue of PLPro which damaged the protease structure, but A889V, a less conserved residue, presumably neutralized that damage. Conclusions Mutants of NSP-1 could provide attenuated vaccines against coronavirus. Also, these mutations of PLPro might be targeted to develop better anti-SARS therapeutics. We hope our study will help to get better insides during the development of attenuated vaccine and PLPro inhibitors.

ABSTRACT A coding-complete genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolate was revealed. The sample for the virus was isolated from a female patient from Dhaka, Bangladesh, suffering from coronavirus disease-2019 (COVID-19).

As the COVID-19 pandemic continues to ravage across the globe and take millions of lives and like many parts of the world, the second wave of the pandemic hit Bangladesh, this study aimed at understanding its causative agent, SARS-CoV-2 at the genomic and proteomic level and provide precious insights about the pathogenesis, evolution, strengths and weaknesses of the virus. As of Mid-June 2021, over 1500 SARS-CoV-2 genomesequences have been deposited in the GISAID database from Bangladesh which were extracted and categorized into two waves. By analyzing these genome sequences, it was discovered that the wave-2 samples had a significantly greater average rate of mutation/sample (30.79%) than the wave-1 samples (12.32%). Wave-2 samples also had a higher frequency of deletion, and transversion events. During the first wave, the GR clade was the most predominant but it was replaced by the GH clade in the latter wave. The B.1.1.25 variant showed the highest frequency in wave-1 while in case of wave-2, the B.1.351.3 variant, was the most common one. A notable presence of the delta variant, which is currently at the center of concern, was also observed. Comparison of the Spike protein found in the reference and the 3 most common lineages found in Bangladesh namely, B.1.1.7, B.1.351, B.1.617 in terms of their ability to form stable complexes with ACE2 receptor revealed that B.1.617 had the potential to be more transmissible than others. Importantly, no indigenous variants have been detected so far which implies that the successful prevention of import of foreign variants can diminish the outbreak in the country.

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GRIN2A is a gene that encodes NMDA receptors found in the central nervous system and plays a pivotal role in excitatory synaptic transmission, plasticity and excitotoxicity in the mammalian central nervous system. Changes in this gene have been associated with a spectrum of neurodevelopmental disorders such as epilepsy. Previous studies on GRIN2A suggest that non-synonymous single nucleotide polymorphisms (nsSNPs) can alter the protein’s structure and function. To gain a better understanding of the impact of potentially deleterious variants of GRIN2A, a range of bioinformatics tools were employed in this study. Out of 1320 nsSNPs retrieved from the NCBI database, initially 16 were predicted as deleterious by 9 tools. Further assessment of their domain association, conservation profile, homology models, interatomic interaction, and Molecular Dynamic Simulation revealed that the variant I463S is likely to be the most deleterious for the structure and function of the protein. Despite the limitations of computational algorithms, our analyses have provided insights that can be a valuable resource for further in vitro and in vivo research on GRIN2A-associated diseases.

Coronavirus disease-2019 has become an immense threat to global public health. The causative agent of this disease is a novel zoonotic pathogen called Severe Acute Respiratory Syndrome related Coronavirus-2 (SARS-CoV-2). Since this is a newly evolved pathogen, very limited information is available to develop effective therapeutics against this deadly virus. Although bioinformatics based analysis could be handy to unveil drugs or vaccines against bacteria and fungus, such approaches are hardly seen for acellular viruses. However, in this study we rationally merged several powerful in silico techniques and proposed prospective therapeutics based on available omics data for COVID-19. Through meticulous analysis of conserved regions of 67 SARS-CoV-2 strains, spike and membrane glycoproteins were chosen to develop and propose a chimeric vaccine against this virus. siRNAs were also designed against these glycoprotein genes to silence them. Moreover, six drug compound candidates were suggested to inhibit the conserved RNA-directed RNA polymerase protein. Finally, due to the close relationship of SARS-CoV-2 and SARS-CoV, publicly available gene expression datasets of SARS-CoV were analyzed to identify 13 immunoregulatory genes that might develop interferon based therapy. Our study will quicken the researches among pharmaceuticals, researchers and clinicians to develop rapid therapeutics for controlling this notorious pandemic disease.

As the COVID-19 pandemic continues to ravage across the globe and take millions of lives, worldwide efforts to understand its causative agent, SARS-CoV-2 at the genomic level are also running in full swing. Such studies are providing precious insights about the pathogenesis, evolution, strengths and weaknesses of the virus. As of October 1st, 2020, 323 SARS-CoV-2 genomes have been sequenced across Bangladesh. The current study is aimed at answering some vital questions about these sequences. From our analyses, it was discovered that the majority of the SARS-CoV-2 found in Bangladesh belonged to the lineage B 1.1.25 of GR clade. Dhaka and Chittagong division were the most diverse in terms of SARS-CoV-2 clades while Mymensing was the least. There are more variety of clades in southern parts of Bangladesh than the northern parts. The most commonly found SARS-CoV-2 mutations found in the country were Spike_D614G, NSP12_P323L, N_G204R and N_R203K. Even though no significant pattern of distribution could be drawn between mutations found in Bangladesh and the countries with similar mortality rates and the countries with large Bangladeshi diaspora, to a certain degree they match with those in the UK, Oman, Italy, Greece, South Africa and Russia. Therefore, careful eye should be kept on the performance of vaccines in those countries in the near future as they are likely to work well in Bangladesh if they work well there. Mutational events in Bangladesh were found to increase between April and July, 2020 and decrease since August, 2020. The number of mutations per SARS-CoV-2 virus sample in Bangladesh was calculated to be 6.88 which is lower than the global average of 7.23. The decrease and the lower rate of mutation raise the possibility of a vaccine or drug working sustainably to protect the people. Based on these insights, a clear picture about the ongoing pandemic can be drawn in the context of Bangladesh which will help the country take appropriate measures to combat the virus.

Coronavirus disease-2019 (COVID-19) has become an immense threat to global public health. The causative agent of this disease is a novel zoonotic pathogen called Severe Acute Respiratory Syndrome related Coronavirus-2 (SARS-CoV-2). Since this is a newly evolved pathogen, very limited information is available to develop effective therapeutics against this deadly virus. Although bioinformatics based analysis could be handy to unveil drugs or vaccines against bacteria and fungus, such approaches are hardly seen for acellular viruses. However, in this study we rationally merged several powerful in silico techniques and proposed prospective therapeutics based on available omics data for COVID-19. Through meticulous analysis of conserved regions of 67 SARS-CoV-2 strains, spike and membrane glycoproteins were chosen to develop and propose a chimeric vaccine against this virus. siRNAs were also designed against these glycoprotein genes to silence them. Moreover, six drug compound candidates were suggested to inhibit the conserved RNA-directed RNA polymerase protein. Finally, due to the close relationship of SARS-CoV-2 and SARS-CoV, publicly available gene expression datasets of SARS-CoV were analyzed to identify 13 immunoregulatory genes that might develop interferon based therapy. Our study will quicken the researches among pharmaceuticals, researchers and clinicians to develop rapid therapeutics for controlling this notorious pandemic disease. Authors Mohammad Uzzal Hossain, Arittra Bhattacharjee, Md. Tabassum Hossain Emon, and Zeshan Mahmud Chowdhury contributed equally to this work.