RESUMEN
We explored the gut microbiome composition in four Moroccan patients with coronavirus disease 2019 (COVID-19) during hospitalization and treatment, using 16S rRNA gene amplicon metataxonomic profiling, and compared it with that in four healthy severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-free control subjects.
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The human transmembrane protease serine 2 (TMPRSS2) protein plays an important role in prostate cancer progression. It also facilitates viral entry into target cells by proteolytically cleaving and activating the S protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the current study, we used different available tools like SIFT, PolyPhen2.0, PROVEAN, SNAP2, PMut, MutPred2, I-Mutant Suite, MUpro, iStable, ConSurf, ModPred, SwissModel, PROCHECK, Verify3D, and TM-align to identify the most deleterious variants and to explore possible effects on the TMPRSS2 stability, structure, and function. The six missense variants tested were evaluated to have deleterious effects on the protein by SIFT, PolyPhen2.0, PROVEAN, SNAP2, and PMut. Additionally, V160M, G181R, R240C, P335L, G432A, and D435Y variants showed a decrease in stability by at least 2 servers; G181R, G432A, and D435Y are highly conserved and identified posttranslational modifications sites (PTMs) for proteolytic cleavage and ADP-ribosylation using ConSurf and ModPred servers. The 3D structure of TMPRSS2 native and mutants was generated using 7 meq as a template from the SwissModeller group, refined by ModRefiner, and validated using the Ramachandran plot. Hence, this paper can be advantageous to understand the association between these missense variants rs12329760, rs781089181, rs762108701, rs1185182900, rs570454392, and rs867186402 and susceptibility to SARS-CoV-2.
Asunto(s)
COVID-19/genética , Mutación Missense , Serina Endopeptidasas/química , Serina Endopeptidasas/genética , Sitios de Unión , Biología Computacional/métodos , Evolución Molecular , Predisposición Genética a la Enfermedad , Humanos , Modelos Moleculares , Filogenia , Polimorfismo de Nucleótido Simple , Conformación Proteica , Estabilidad Proteica , Serina Endopeptidasas/metabolismoRESUMEN
SARS-CoV-2 coronavirus uses for entry to human host cells a SARS-CoV receptor of the angiotensin-converting enzyme (ACE2) that catalyzes the conversion of angiotensin II into angiotensin (1-7). To understand the effect of ACE2 missense variants on protein structure, stability, and function, various bioinformatics tools were used including SIFT, PANTHER, PROVEAN, PolyPhen2.0, I. Mutant Suite, MUpro, SWISS-MODEL, Project HOPE, ModPred, QMEAN, ConSurf, and STRING. All twelve ACE2 nsSNPs were analyzed. Six ACE2 high-risk pathogenic nsSNPs (D427Y, R514G, R708W, R710C, R716C, and R768W) were found to be the most damaging by at least six software tools (cumulative score between 6 and 7) and exert deleterious effect on the ACE2 protein structure and likely function. Additionally, they revealed high conservation, less stability, and having a role in posttranslation modifications such a proteolytic cleavage or ADP-ribosylation. This in silico analysis provides information about functional nucleotide variants that have an impact on the ACE2 protein structure and function and therefore susceptibility to SARS-CoV-2.
Asunto(s)
Enzima Convertidora de Angiotensina 2/genética , COVID-19/genética , Predisposición Genética a la Enfermedad/genética , Mutación Missense/genética , Algoritmos , Enzima Convertidora de Angiotensina 2/química , Enzima Convertidora de Angiotensina 2/metabolismo , Biología Computacional , Simulación por Computador , Humanos , Polimorfismo de Nucleótido Simple/genética , SARS-CoV-2/química , SARS-CoV-2/metabolismoRESUMEN
Over the last decade, it has become increasingly apparent that the microbiome is a central component in human well-being and illness. However, to establish innovative therapeutic methods, it is crucial to learn more about the microbiota. Thereby, the area of metagenomics and associated bioinformatics methods and tools has become considerable in the study of the human microbiome biodiversity. The application of these metagenomics approaches to studying the gut microbiome in COVID-19 patients could be one of the promising areas of research in the fight against the SARS-CoV-2 infection and disparity. Therefore, understanding how the gut microbiome is affected by or could affect the SARS-CoV-2 is very important. Herein, we present an overview of approaches and methods used in the current published studies on COVID-19 patients and the gut microbiome. The accuracy of these researches depends on the appropriate choice and the optimal use of the metagenomics bioinformatics platforms and tools. Interestingly, most studies reported that COVID-19 patients' microbiota are enriched with opportunistic microorganisms. The choice and use of appropriate computational tools and techniques to accurately investigate the gut microbiota is therefore critical in determining the appropriate microbiome profile for diagnosis and the most reliable antiviral or preventive microbial composition.
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INTRODUCTION: SARS-Cov-2 first appeared in Wuhan, China, in December 2019 and spread all over the world soon after that. Given the infectious nature ofSARS-CoV-2, fast and accurate diagnosis tools are important to detect the virus. In this review, we discuss the different diagnostic tests that are currently being implemented in laboratories and provide a description of various COVID-19 kits. AREAS COVERED: We summarize molecular techniques that target the viral load, serological methods used for SARS-CoV-2 specific antibodies detection as well as newly developed faster assays for the detection of SARS-COV 2 in various biological samples. EXPERT OPINION: In the light of the widespread pandemic, the massive diagnosis of COVID-19, using various detection techniques, appears to be the most effective strategy for monitoring and containing its propagation.