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1.
iScience ; 25(3): 103880, 2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35156006

RESUMO

There is a dearth of information on COVID-19 disease dynamics in Africa. To fill this gap, we investigated the epidemiology and genetic diversity of SARS-CoV-2 lineages circulating in the continent. We retrieved 5229 complete genomes collected in 33 African countries from the GISAID database. We investigated the circulating diversity, reconstructed the viral evolutionary divergence and history, and studied the case and death trends in the continent. Almost a fifth (144/782, 18.4%) of Pango lineages found worldwide circulated in Africa, with five different lineages dominating over time. Phylogenetic analysis revealed that African viruses cluster more closely with those from Europe. We also identified two motifs that could function as integrin-binding sites and N-glycosylation domains. These results shed light on the epidemiological and evolutionary dynamics of the circulating viral diversity in Africa. They also emphasize the need to expand surveillance efforts in Africa to help inform and implement better public health measures.

2.
medRxiv ; 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34031660

RESUMO

COVID-19 disease dynamics have been widely studied in different settings around the globe, but little is known about these patterns in the African continent. To investigate the epidemiology and genetic diversity of SARS-CoV-2 lineages circulating in Africa, more than 2400 complete genomes from 33 African countries were retrieved from the GISAID database and analyzed. We investigated their diversity using various clade and lineage nomenclature systems, reconstructed their evolutionary divergence and history using maximum likelihood inference methods, and studied the case and death trends in the continent. We also examined potential repeat patterns and motifs across the sequences. In this study, we show that after almost one year of the COVID-19 pandemic, only 143 out of the 782 Pango lineages found worldwide circulated in Africa, with five different lineages dominating in distinct periods of the pandemic. Analysis of the number of reported deaths in Africa also revealed large heterogeneity across the continent. Phylogenetic analysis revealed that African viruses cluster closely with those from all continents but more notably with viruses from Europe. However, the extent of viral diversity observed among African genomes is closest to that of the Oceania outbreak, most likely due to genomic under-surveillance in Africa. We also identified two motifs that could function as integrin-binding sites and N-glycosylation domains. These results shed light on the evolutionary dynamics of the circulating viral strains in Africa, elucidate the functions of protein motifs present in the genome sequences, and emphasize the need to expand genomic surveillance efforts in the continent to better understand the molecular, evolutionary, epidemiological, and spatiotemporal dynamics of the COVID-19 pandemic in Africa.

3.
Mol Biotechnol ; 63(4): 267-288, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33523418

RESUMO

Current research energies are fixated on the synthesis of environmentally friendly and non-hazardous products, which include finding and recognizing biosurfactants that can substitute synthetic surfactants. Microbial biosurfactants are surface-active compounds synthesized intracellularly or extracellularly. To use biosurfactants in various industries, it is essential to understand scientific engagements that demonstrate its potentials as real advancement in the 21st century. Other than applying a substantial effect on the world economic market, engineered hyper-producing microbial strains in combination with optimized cultivation parameters have made it probable for many industrial companies to receive the profits of 'green' biosurfactant innovation. There needs to be an emphasis on the worldwide state of biosurfactant synthesis, expression of biosurfactant genes in expressive host systems, the recent developments, and prospects in this line of research. Thus, molecular dynamics with respect to genetic engineering of biosynthetic genes are proposed as new biotechnological tools for development, improved synthesis, and applications of biosurfactants. For example, mutant and hyper-producing recombinants have been designed efficaciously to advance the nature, quantity, and quality of biosurfactants. The fastidious and deliberate investigation will prompt a comprehension of the molecular dynamics and phenomena in new microorganisms. Throughout the decade, valuable data on the molecular genetics of biosurfactant have been produced, and this solid foundation would encourage application-oriented yields of the biosurfactant production industry and expand its utilization in diverse fields. Therefore, the conversations among different interdisciplinary experts from various scientific interests such as microbiology, biochemistry, molecular biology, and genetics are indispensable and significant to accomplish these objectives.


Assuntos
Bactérias/crescimento & desenvolvimento , Engenharia Genética/métodos , Tensoativos/metabolismo , Bactérias/genética , Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Vias Biossintéticas , Mutação , Proteínas Recombinantes/metabolismo
4.
Inform Med Unlocked ; 21: 100438, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33043110

RESUMO

Stimulation and generation of T and B cell-mediated long-term immune response are essential for the curbing of a deadly virus such as SAR-CoV-2 (Severe Acute Respiratory Corona Virus 2). Immunoinformatics approach in vaccine design takes advantage of antigenic and non-allergenic epitopes present on the spike glycoprotein of SARS-CoV-2 to elicit immune responses. T cells and B cells epitopes were predicted, and the selected residues were subjected to allergenicity, antigenicity and toxicity screening which were linked by appropriate linkers to form a multi-epitope subunit vaccine. The physiochemical properties of the vaccine construct were analyzed, and the molecular weight, molecular formula, theoretical isoelectric point value, half-life, solubility score, instability index, aliphatic index and GRAVY were predicted. The vaccine structure was constructed, refined, validated, and disulfide engineered to get the best model. Molecular binding simulation and molecular dynamics simulation were carried out to predict the stability and binding affinity of the vaccine construct with TLRs. Codon acclimatization and in silico cloning were performed to confirm the vaccine expression and potency. Results obtained indicated that this novel vaccine candidate is non-toxic, capable of initiating the immunogenic response and will not induce an allergic reaction. The highest binding energy was observed in TLR4 (Toll-like Receptor 4) (-1398.1), and the least is TLR 2 (-1479.6). The steady rise in Th (T-helper) cell population with memory development was noticed, and IFN-g (Interferon gamma) was provoked after simulation. At this point, the vaccine candidate awaits animal trial to validate its efficacy and safety for use in the prevention of the novel COVID-19 (Coronavirus Disease 2019) infections.

5.
Biochem Mol Biol Educ ; 47(6): 620-631, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31520514

RESUMO

Bioinformatics was recently introduced as a module for both undergraduate and postgraduate biological sciences students at our institution. Our experience shows that inquiry-based hands-on exercises provide the most efficient approach to bioinformatic straining. In this article, we report a structural bioinformatics project carried out by Master degree students to determine structure-function relationships of the uncharacterized prokaryotic 5-oxoprolinase subunit A (PxpA). PxpA associates with the PxpBC complex to form a functional 5-oxoprolinase enzyme for conversion of 5-oxoproline to L-glutamate. Although the exact role of PxpA is yet to be determined, it has been demonstrated that PxpBC catalyses the first step of the reaction, which is phosphorylation of 5-oxoproline. Here, we provide evidence that PxpA is involved in the last two steps of the reaction:decyclization of the labile phosphorylated 5-oxoproline to the equally labile γ-glutamylphosphate, and subsequent dephosphorylation to L-glutamate. Structural bioinformatics analysis of four putative PxpA structures revealed that PxpA adopts a non-canonical TIM barrel fold with well-characterized TIM barrel enzyme features. These include a C-terminal groove comprising potentially essential conserved amino acid residues organized into putative motifs. Phylogenetic analysis suggests a relationship between taxonomic grouping and PxpA oligomerization. PxpA forms a tunnel upon ligand binding, thus suggesting that the PxpABC complex employs the mechanism of substrate channeling to protect labile intermediates. Ultimately, students were able to form a testable hypothesis on the function of PxpA, an achievement we consider encouraging other students to emulate. © 2019 International Union of Biochemistry and Molecular Biology, 47(6):620-631, 2019.


Assuntos
Disciplinas das Ciências Biológicas/educação , Biologia Computacional/educação , Piroglutamato Hidrolase/química , Piroglutamato Hidrolase/metabolismo , Currículo , Ácido Glutâmico/química , Ácido Glutâmico/metabolismo , Humanos , Modelos Moleculares , Ácido Pirrolidonocarboxílico/química , Ácido Pirrolidonocarboxílico/metabolismo , Relação Estrutura-Atividade , Estudantes
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