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1.
Artículo en Inglés | MEDLINE | ID: mdl-34665737

RESUMEN

Bridging Centrality (BriCe) is a measure that combines the Betweenness centrality and Bridging coefficient metrics to characterize nodes acting as a bridge among clusters. However, there were no implementations of the BriCe plugin that can be readily used in the GEPHI software or any other software dedicated to graph-based studies. We present the BriCe plugin for GEPHI. It is available as a third-party functionality from the native GEPHI interface as a handy plugin to add; hence, no additional download and installation process is necessary. The BriCe plugin for GEPHI is open-source, and one can access the code through the GEPHI GitHub repository. As a use case of the BriCe plugin, we analyzed the genome of Mycobacterium tuberculosis H37Rv to identify biological explanations on why some proteins were ranked with top BriCe values For instance, we were able to formulate a new hypothesis combining the predicted subcellular localization and high BriCe values concerning lipopolysaccharides (LPS) exportation. Our hypothesis provides a possible link among proteins of a glycosyltransferase group and the type VII Secretion System. The Bridging Centrality plugin for GEPHI is an easy to use tool for analyzing complex graphs and draw novel insights from graphical data.

2.
Sci Rep ; 11(1): 17689, 2021 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-34480062

RESUMEN

COVID-19, a global pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 virus, has claimed millions of lives worldwide. Amid soaring contagion due to newer strains of the virus, it is imperative to design dynamic, spatiotemporal models to contain the spread of infection during future outbreaks of the same or variants of the virus. The reliance on existing prediction and contact tracing approaches on prior knowledge of inter- or intra-zone mobility renders them impracticable. We present a spatiotemporal approach that employs a network inference approach with sliding time windows solely on the date and number of daily infection numbers of zones within a geographical region to generate temporal networks capturing the influence of each zone on another. It helps analyze the spatial interaction among the hotspot or spreader zones and highly affected zones based on the flow of network contagion traffic. We apply the proposed approach to the daily infection counts of New York State as well as the states of USA to show that it effectively measures the phase shifts in the pandemic timeline. It identifies the spreaders and affected zones at different time points and helps infer the trajectory of the pandemic spread across the country. A small set of zones periodically exhibit a very high outflow of contagion traffic over time, suggesting that they act as the key spreaders of infection. Moreover, the strong influence between the majority of non-neighbor regions suggests that the overall spread of infection is a result of the unavoidable long-distance trips by a large number of people as opposed to the shorter trips at a county level, thereby informing future mitigation measures and public policies.


Asunto(s)
COVID-19 , Trazado de Contacto , Bases de Datos Factuales , Pandemias , COVID-19/epidemiología , COVID-19/transmisión , Humanos , New York/epidemiología , Salud Pública , SARS-CoV-2
3.
Biomolecules ; 11(9)2021 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-34572488

RESUMEN

Cardiac glycosides are natural sterols and constitute a group of secondary metabolites isolated from plants and animals. These cardiotonic agents are well recognized and accepted in the treatment of various cardiac diseases as they can increase the rate of cardiac contractions by acting on the cellular sodium potassium ATPase pump. However, a growing number of recent efforts were focused on exploring the antitumor and antiviral potential of these compounds. Several reports suggest their antitumor properties and hence, today cardiac glycosides (CG) represent the most diversified naturally derived compounds strongly recommended for the treatment of various cancers. Mutated or dysregulated transcription factors have also gained prominence as potential therapeutic targets that can be selectively targeted. Thus, we have explored the recent advances in CGs mediated cancer scope and have considered various signaling pathways, molecular aberration, transcription factors (TFs), and oncogenic genes to highlight potential therapeutic targets in cancer management.

4.
Front Immunol ; 12: 663912, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34305894

RESUMEN

The Spike (S) protein of the SARS-CoV-2 virus is critical for its ability to attach and fuse into the host cells, leading to infection, and transmission. In this review, we have initially performed a meta-analysis of keywords associated with the S protein to frame the outline of important research findings and directions related to it. Based on this outline, we have reviewed the structure, uniqueness, and origin of the S protein of SARS-CoV-2. Furthermore, the interactions of the Spike protein with host and its implications in COVID-19 pathogenesis, as well as drug and vaccine development, are discussed. We have also summarized the recent advances in detection methods using S protein-based RT-PCR, ELISA, point-of-care lateral flow immunoassay, and graphene-based field-effect transistor (FET) biosensors. Finally, we have also discussed the emerging Spike mutants and the efficacy of the Spike-based vaccines against those strains. Overall, we have covered most of the recent advances on the SARS-CoV-2 Spike protein and its possible implications in countering this virus.


Asunto(s)
SARS-CoV-2/metabolismo , Glicoproteína de la Espiga del Coronavirus/metabolismo , COVID-19/diagnóstico , COVID-19/tratamiento farmacológico , COVID-19/prevención & control , COVID-19/virología , Prueba de COVID-19 , Vacunas contra la COVID-19/inmunología , Interacciones Huésped-Patógeno , Humanos , Mutación , SARS-CoV-2/genética , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , Especificidad de la Especie , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunología
5.
Gene ; 795: 145781, 2021 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-34153410

RESUMEN

The Bifidobacterium longum 51A strain of isolated from feces of a healthy child, has demonstrated probiotic properties by in vivo and in vitro studies, which may be assigned to its production of metabolites such as acetate. Thus, through the study of comparative genomics, the present work sought to identify unique genes that might be related to the production of acetate. To perform the study, the DNA strain was sequenced using Illumina HiSeq technology, followed by assembly and manual curation of coding sequences. Comparative analysis was performed including 19 complete B. longum genomes available in Genbank/NCBI. In the phylogenetic analysis, the CECT 7210 and 157F strains of B. longum subsp. infantis aggregated within the subsp. longum cluster, suggesting that their taxonomic classification should be reviewed. The strain 51A of B. longum has 26 unique genes, six of which are possibly related to carbohydrate metabolism and acetate production. The phosphoketolase pathway from B. longum 51A showed a difference in acetyl-phosphate production. This result seems to corroborate the analysis of their unique genes, whose presence suggests the strain may use different sources of carbohydrates that allow a greater production of acetate and consequently offer benefits to the host health.


Asunto(s)
Acetatos/metabolismo , Bifidobacterium longum/genética , Bifidobacterium longum/metabolismo , Metabolismo de los Hidratos de Carbono/genética , Genes Bacterianos , Probióticos/metabolismo , Secuencia de Bases , Bifidobacterium longum/clasificación , Niño , Simulación por Computador , Heces/microbiología , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Filogenia , Análisis de Secuencia de ADN
6.
Genomics ; 113(4): 2730-2743, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34118385

RESUMEN

Mycoplasma genitalium is an obligate intracellular bacterium that is responsible for several sexually transmitted infections, including non-gonococcal urethritis in men and several inflammatory reproductive tract syndromes in women. Here, we applied subtractive genomics and reverse vaccinology approaches for in silico prediction of potential vaccine and drug targets against five strains of M. genitalium. We identified 403 genes shared by all five strains, from which 104 non-host homologous proteins were selected, comprising of 44 exposed/secreted/membrane proteins and 60 cytoplasmic proteins. Based on the essentiality, functionality, and structure-based binding affinity, we finally predicted 19 (14 novel) putative vaccine and 7 (2 novel) candidate drug targets. The docking analysis showed six molecules from the ZINC database as promising drug candidates against the identified targets. Altogether, both vaccine candidates and drug targets identified here may contribute to the future development of therapeutic strategies to control the spread of M. genitalium worldwide.

7.
J Appl Clin Med Phys ; 22(7): 177-187, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34101349

RESUMEN

Rigorous radiotherapy quality surveillance and comprehensive outcome assessment require electronic capture and automatic abstraction of clinical, radiation treatment planning, and delivery data. We present the design and implementation framework of an integrated data abstraction, aggregation, and storage, curation, and analytics software: the Health Information Gateway and Exchange (HINGE), which collates data for cancer patients receiving radiotherapy. The HINGE software abstracts structured DICOM-RT data from the treatment planning system (TPS), treatment data from the treatment management system (TMS), and clinical data from the electronic health records (EHRs). HINGE software has disease site-specific "Smart" templates that facilitate the entry of relevant clinical information by physicians and clinical staff in a discrete manner as part of the routine clinical documentation. Radiotherapy data abstracted from these disparate sources and the smart templates are processed for quality and outcome assessment. The predictive data analyses are done on using well-defined clinical and dosimetry quality measures defined by disease site experts in radiation oncology. HINGE application software connects seamlessly to the local IT/medical infrastructure via interfaces and cloud services and performs data extraction and aggregation functions without human intervention. It provides tools to assess variations in radiation oncology practices and outcomes and determines gaps in radiotherapy quality delivered by each provider.


Asunto(s)
Neoplasias , Oncología por Radiación , Documentación , Humanos , Neoplasias/radioterapia , Planificación de la Radioterapia Asistida por Computador , Programas Informáticos
8.
Soc Sci Humanit Open ; 3(1): 100098, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34173505

RESUMEN

Lockdown measures to curb the spread of COVID-19 has brought the world economy on the brink of a recession. It is imperative that nations formulate administrative policies based on the changing economic landscape. In this work, we apply a statistical approach, called topic modeling, on text documents of job loss notices of 26 US states to identify the specific states and industrial sectors affected economically by this ongoing public health crisis. Our analysis reveals that there is a considerable incongruity in job loss patterns between the pre- and during-COVID timelines in several states and the recreational and philanthropic sectors register high job losses. It further shows that the interplay among several possible socioeconomic factors would lead to job losses in many sectors, while also creating new job opportunities in other sectors such as public service, pharmaceuticals and media, making the job loss trends a key indicator of the world economy. Finally, we compare the low income job loss rates against overall job losses due to COVID-19 in the US counties, and discuss the implications of press reports on reopening businesses and the unemployed workforce being absorbed by other sectors.

9.
Soc Sci Humanit Open ; : 100163, 2021 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-33997770

RESUMEN

COVID-19, declared by the World Health Organization as a Public Health Emergency of International Concern, has claimed over 2.7 million lives worldwide. In the absence of vaccinations, social distancing and lockdowns emerged as the means to curb infection spread, with the downside of bringing the world economy to a standstill. In this work, we explore the epidemiological, socioeconomic and demographic factors affecting the unemployment rates of United States that may contribute towards policymaking to contain contagion and mortality while balancing the economy in the future. We identify the ethnic groups and job sectors that are affected by the pandemic and demonstrate that Gross Domestic Product (GDP), race, age group, lockdown severity and infected count are the key indicators of post-COVID job loss trends.

10.
Viruses ; 13(4)2021 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-33919537

RESUMEN

The COVID-19 pandemic has infected millions worldwide, leaving a global burden for long-term care of COVID-19 survivors. It is thus imperative to study post-COVID (i.e., short-term) and long-COVID (i.e., long-term) effects, specifically as local and systemic pathophysiological outcomes of other coronavirus-related diseases (such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS)) were well-cataloged. We conducted a comprehensive review of adverse post-COVID health outcomes and potential long-COVID effects. We observed that such adverse outcomes were not localized. Rather, they affected different human systems, including: (i) immune system (e.g., Guillain-Barré syndrome, rheumatoid arthritis, pediatric inflammatory multisystem syndromes such as Kawasaki disease), (ii) hematological system (vascular hemostasis, blood coagulation), (iii) pulmonary system (respiratory failure, pulmonary thromboembolism, pulmonary embolism, pneumonia, pulmonary vascular damage, pulmonary fibrosis), (iv) cardiovascular system (myocardial hypertrophy, coronary artery atherosclerosis, focal myocardial fibrosis, acute myocardial infarction, cardiac hypertrophy), (v) gastrointestinal, hepatic, and renal systems (diarrhea, nausea/vomiting, abdominal pain, anorexia, acid reflux, gastrointestinal hemorrhage, lack of appetite/constipation), (vi) skeletomuscular system (immune-mediated skin diseases, psoriasis, lupus), (vii) nervous system (loss of taste/smell/hearing, headaches, spasms, convulsions, confusion, visual impairment, nerve pain, dizziness, impaired consciousness, nausea/vomiting, hemiplegia, ataxia, stroke, cerebral hemorrhage), (viii) mental health (stress, depression and anxiety). We additionally hypothesized mechanisms of action by investigating possible molecular mechanisms associated with these disease outcomes/symptoms. Overall, the COVID-19 pathology is still characterized by cytokine storm that results to endothelial inflammation, microvascular thrombosis, and multiple organ failures.


Asunto(s)
COVID-19/complicaciones , COVID-19/fisiopatología , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/fisiopatología , Sistema Cardiovascular , Diarrea , Síndrome de Guillain-Barré , Hemostasis , Humanos , Sistema Inmunológico , Inflamación , Salud Mental , Sistema Nervioso , Pandemias , SARS-CoV-2 , Síndrome Respiratorio Agudo Grave , Trombosis
11.
Astrobiology ; 21(6): 706-717, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33646011

RESUMEN

Cellulose is a widespread macromolecule in terrestrial environments and a major architectural component of microbial biofilm. Therefore, cellulose might be considered a biosignature that indicates the presence of microbial life. We present, for the first time, characteristics of bacterial cellulose after long-term spaceflight and exposure to simuled Mars-like stressors. The pristine cellulose-based pellicle membranes from a kombucha microbial community (KMC) were exposed outside the International Space Station, and after their return to Earth, the samples were reactivated and cultured for 2.5 years to discern whether the KMC could be restored. Analyses of cellulose polymer integrity and mechanical properties of cellulose-based pellicle films, as well as the cellulose biosynthesis-related genes' structure and expression, were performed. We observed that (i) the cellulose polymer integrity was not significantly changed under Mars-like conditions; (ii) de novo cellulose production was 1.5 times decreased in exposed KMC samples; (iii) the dry cellulose yield from the reisolated Komagataeibacter oboediens was 1.7 times lower than by wild type; (iv) there was no significant change in mechanical properties of the de novo synthesized cellulose-based pellicles produced by the exposed KMCs and K. oboediens; and (v) the gene, encoding biosynthesis of cellulose (bcsA) of the K. oboediens, was downregulated, and no topological change or mutation was observed in any of the bcs operon genes, indicating that the decreased cellulose production by the space-exposed samples was probably due to epigenetic regulation. Our results suggest that the cellulose-based pellicle could be a good material with which to protect microbial communities during space journeys, and the cellulose produced by KMC members could be suitable in the fabrication of consumer goods for extraterrestrial locations.

12.
Mol Omics ; 17(2): 317-337, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33683246

RESUMEN

Comprehensive clinical pictures, comorbid conditions, and long-term complications of COVID-19 are still unknown. Recently, using a multi-omics-based strategy, we predicted potential drugs for COVID-19 with ∼70% accuracy. Herein, using a novel multi-omics-based bioinformatic approach and three ways of analysis, we identified the symptoms, comorbid conditions, and short-, mid-, and possible long-term complications of COVID-19 with >90% precision including 27 parent, 170 child, and 403 specific conditions. Among the specific conditions, 36 viral, 53 short-term, 62 short-mid-long-term, 194 mid-long-term, and 57 congenital conditions are identified. At a threshold "count of occurrence" of 4, we found that 83-100% (average 92.67%) of enriched conditions are associated with COVID-19. Except for dry cough and loss of taste, all the other COVID-19-associated mild and severe symptoms are enriched. CVDs, and pulmonary, metabolic, musculoskeletal, neuropsychiatric, kidney, liver, and immune system disorders are top comorbid conditions. Specific diseases like myocardial infarction, hypertension, COPD, lung injury, diabetes, cirrhosis, mood disorders, dementia, macular degeneration, chronic kidney disease, lupus, arthritis, etc. along with several other NCDs were found to be top candidates. Interestingly, many cancers and congenital disorders associated with COVID-19 severity are also identified. Arthritis, gliomas, diabetes, psychiatric disorders, and CVDs having a bidirectional relationship with COVID-19 are also identified as top conditions. Based on our accuracy (>90%), the long-term presence of SARS-CoV-2 RNA in human, and our "genetic remittance" assumption, we hypothesize that all the identified top-ranked conditions could be potential long-term consequences in COVID-19 survivors, warranting long-term observational studies.


Asunto(s)
COVID-19/complicaciones , COVID-19/fisiopatología , Genómica/métodos , COVID-19/genética , COVID-19/metabolismo , Comorbilidad , Humanos , Índice de Severidad de la Enfermedad
13.
J Comput Biol ; 28(2): 166-184, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32985908

RESUMEN

Clinical factors, including T-stage, Gleason score, and baseline prostate-specific antigen, are used to stratify patients with prostate cancer (PCa) into risk groups. This provides prognostic information for a heterogeneous disease such as PCa and guides treatment selection. In this article, we hypothesize that nonclinical factors may also impact treatment selection and their adherence to treatment guidelines. A total of 552 patients with intermediate- and high-risk PCa treated with definitive radiation with or without androgen deprivation therapy (ADT) between 2010 and 2017 were identified from 34 medical centers within the Veterans Health Administration. Medical charts were manually reviewed, and details regarding each patient's clinical history and treatment were extracted. Support Vector Machine and Random forest-based classification was used to identify clinical and nonclinical predictors of adherence to the treatment guidelines from the National Comprehensive Cancer Network (NCCN). We created models for predicting both initial treatment intent and treatment alterations. Our results demonstrate that besides clinical factors, the center in which the patient was treated (nonclinical factor) played a significant role in adherence to NCCN guidelines. Furthermore, the treatment center served as an important predictor to decide on whether or not to prescribe ADT; however, it was not associated with ADT duration and weakly associated with treatment alterations. Such center-bias motivates further investigation on details of center-specific barriers to both NCCN guideline adherence and on oncological outcomes. In addition, we demonstrate that publicly available data sets, for example, that from Surveillance, Epidemiology, and End Results (SEERs), may not be well equipped to build such predictive models on treatment plans.

14.
J. venom. anim. toxins incl. trop. dis ; 27: e20200027, 2021. tab, graf
Artículo en Inglés | ID: biblio-1287091

RESUMEN

Mycobacterium leprae and Mycobacterium lepromatosis are gram-positive bacterial pathogens and the causative agents of leprosy in humans across the world. The elimination of leprosy cannot be achieved by multidrug therapy alone, and highlights the need for new tools and drugs to prevent the emergence of new resistant strains. Methods In this study, our contribution includes the prediction of vaccine targets and new putative drugs against leprosy, using reverse vaccinology and subtractive genomics. Six strains of Mycobacterium leprae and Mycobacterium lepromatosis (4 and 2 strains, respectively) were used for comparison taking Mycobacterium leprae strain TN as the reference genome. Briefly, we used a combined reverse vaccinology and subtractive genomics approach. Results As a result, we identified 12 common putative antigenic proteins as vaccine targets and three common drug targets against Mycobacterium leprae and Mycobacterium lepromatosis. Furthermore, the docking analysis using 28 natural compounds with three drug targets was done. Conclusions The bis-naphthoquinone compound Diospyrin (CID 308140) obtained from indigenous plant Diospyros spp. showed the most favored binding affinity against predicted drug targets, which can be a candidate therapeutic target in the future against leprosy.(AU)


Asunto(s)
Bacilos Grampositivos/patogenicidad , Vacunología , Mycobacterium leprae/patogenicidad , Mycobacterium lepraemurium/patogenicidad
16.
Gene ; 772: 145386, 2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33373662

RESUMEN

The emergence of community acquired infections increases the public health concern on K. pneumoniae and closely related bacteria among which antimicrobial resistance spreads. We report a multidrug-resistant K. pneumoniae isolate, B31, of a patient infected in the community and admitted to an intensive care unit in Northeast Brazil. Antimicrobial susceptibility and genome information were thoroughly investigated to characterize B31 in front of 172 sequenced strains of different countries. Assigned to the Sequence Type 15, which is globally spread, B31 presented extended spectrum beta-lactamase, tigecycline and ciprofloxacin resistance. Genome sequencing revealed most resistance genes being carried by plasmids with high dissemination potential. The absence of main virulence factors, like yersiniabactin and colibactin, apparently suggests a mild pathogenic strain which, on the contrary, persisted and caused severe infection in a previously healthy patient. The present study contributes to unveil the unclear genomic scenario of virulent and multidrug-resistant K. pneumoniae in Brazil.


Asunto(s)
Infecciones Comunitarias Adquiridas/microbiología , Farmacorresistencia Bacteriana Múltiple , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/clasificación , Secuenciación Completa del Genoma/métodos , Adulto , Ciprofloxacina/farmacología , Femenino , Genoma Bacteriano , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Klebsiella pneumoniae/genética , Tipificación de Secuencias Multilocus , Plásmidos/genética , Tigeciclina/farmacología
17.
PLoS One ; 15(12): e0244210, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33347470

RESUMEN

The bacterial strain PO100/5 was isolated from a skin abscess taken from a pig (Sus scrofa domesticus) in the Alentejo region of southern Portugal. It was identified as Corynebacterium pseudotuberculosis using biochemical tests, multiplex PCR and Pulsed Field Gel Electrophoresis. After genome sequencing and rpoB phylogeny, the strain was classified as C. ulcerans. To better understand the taxonomy of this strain and improve identification methods, we compared strain PO100/5 to other publicly available genomes from C. diphtheriae group. Taxonomic analysis reclassified it and three others strains as the recently described C. silvaticum, which have been isolated from wild boar and roe deer in Germany and Austria. The results showed that PO100/5 is the first sequenced genome of a C. silvaticum strain from livestock and a different geographical region, has the unique sequence type ST709, and could be could produce the diphtheriae toxin, along with strain 05-13. Genomic analysis of PO100/5 showed four prophages, and eight conserved genomic islands in comparison to C. ulcerans. Pangenome analysis of 38 C. silvaticum and 76 C. ulcerans genomes suggested that C. silvaticum is a genetically homogeneous species, with 73.6% of its genes conserved and a pangenome near to be closed (α > 0.952). There are 172 genes that are unique to C. silvaticum in comparison to C. ulcerans. Most of these conserved genes are related to nutrient uptake and metabolism, prophages or immunity against them, and could be genetic markers for species identification. Strains PO100/5 (livestock) and KL0182T (wild boar) were predicted to be potential human pathogens. This information may be useful for identification and surveillance of this pathogen.


Asunto(s)
Corynebacterium/genética , Ecosistema , Genoma Bacteriano , Filogenia , Corynebacterium/clasificación , Corynebacterium/metabolismo , Marcadores Genéticos , Filogeografía , Polimorfismo Genético
18.
Comput Biol Med ; 126: 104051, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33131530

RESUMEN

SARS-CoV-2 has ushered a global pandemic with no effective drug being available at present. Although several FDA-approved drugs are currently under clinical trials for drug repositioning, there is an on-going global effort for new drug identification. In this paper, using multi-omics (interactome, proteome, transcriptome, and bibliome) data and subsequent integrated analysis, we present the biological events associated with SARS-CoV-2 infection and identify several candidate drugs against this viral disease. We found that: (i) Interactome-based infection pathways differ from the other three omics-based profiles. (ii) Viral process, mRNA splicing, cytokine and interferon signaling, and ubiquitin mediated proteolysis are important pathways in SARS-CoV-2 infection. (iii) SARS-CoV-2 infection also shares pathways with Influenza A, Epstein-Barr virus, HTLV-I, Measles, and Hepatitis virus. (iv) Further, bacterial, parasitic, and protozoan infection pathways such as Tuberculosis, Malaria, and Leishmaniasis are also shared by this virus. (v) A total of 50 candidate drugs, including the prophylaxis agents and pathway specific inhibitors are identified against COVID-19. (vi) Betamethasone, Estrogen, Simvastatin, Hydrocortisone, Tositumomab, Cyclosporin A etc. are among the important drugs. (vii) Ozone, Nitric oxide, plasma components, and photosensitizer drugs are also identified as possible therapeutic candidates. (viii) Curcumin, Retinoic acids, Vitamin D, Arsenic, Copper, and Zinc may be the candidate prophylaxis agents. Nearly 70% of our identified agents are previously suggested to have anti-COVID-19 effects or under clinical trials. Among our identified drugs, the ones that are not yet tested, need validation with caution while an appropriate drug combination from these candidate drugs along with a SARS-CoV-2 specific antiviral agent is needed for effective COVID-19 management.


Asunto(s)
Antivirales , Betacoronavirus , Infecciones por Coronavirus , Bases de Datos Genéticas , Descubrimiento de Drogas , Modelos Biológicos , Pandemias , Neumonía Viral , Antivirales/química , Antivirales/farmacocinética , Antivirales/uso terapéutico , Betacoronavirus/genética , Betacoronavirus/metabolismo , COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/metabolismo , Humanos , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/genética , Neumonía Viral/metabolismo , Proteómica , SARS-CoV-2
19.
Front Genet ; 11: 563975, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33240317

RESUMEN

A multitude of factors, such as drug misuse, lack of strong regulatory measures, improper sewage disposal, and low-quality medicine and medications, have been attributed to the emergence of drug resistant microbes. The emergence and outbreaks of multidrug resistance to last-line antibiotics has become quite common. This is further fueled by the slow rate of drug development and the lack of effective resistome surveillance systems. In this review, we provide insights into the recent advances made in computational approaches for the surveillance of antibiotic resistomes, as well as experimental formulation of combinatorial drugs. We explore the multiple roles of antibiotics in nature and the current status of combinatorial and adjuvant-based antibiotic treatments with nanoparticles, phytochemical, and other non-antibiotics based on synergetic effects. Furthermore, advancements in machine learning algorithms could also be applied to combat the spread of antibiotic resistance. Development of resistance to new antibiotics is quite rapid. Hence, we review the recent literature on discoveries of novel antibiotic resistant genes though shotgun and expression-based metagenomics. To decelerate the spread of antibiotic resistant genes, surveillance of the resistome is of utmost importance. Therefore, we discuss integrative applications of whole-genome sequencing and metagenomics together with machine learning models as a means for state-of-the-art surveillance of the antibiotic resistome. We further explore the interactions and negative effects between antibiotics and microbiomes upon drug administration.

20.
An Acad Bras Cienc ; 92(suppl 2): e20201216, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33084762

RESUMEN

Staphylococcus aureus (S. aureus) is a highly versatile Gram-positive bacterium that is carried asymptomatically by up to 30% of healthy people, while being a major cause of healthcare-associated infections, making it a worldwide problem in clinical medicine. The adaptive evolution of S. aureus strains is demonstrated by its remarkable capacity to promptly develop high resistance to multiple antibiotics, thus limiting treatment choice. Nowadays, there is a continuous demand for an alternative to the use of antibiotics for S. aureus infections and a strategy to control the spread or to kill phylogenetically related strains. In this scenario, bacteriocins fit as with a promising and interesting alternative. These molecules are produced by a range of bacteria, defined as ribosomally synthesized peptides with bacteriostatic or bactericidal activity against a wide range of pathogens. This work reviews ascertained the main antibiotic-resistance mechanisms of S. aureus strains and the current, informative content concerning the applicability of the use of bacteriocins overlapping the use of conventional antibiotics in the context of S. aureus infections. Besides, we highlight the possible application of these biomolecules on an industrial scale in future work.


Asunto(s)
Bacteriocinas , Infecciones Estafilocócicas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias Grampositivas , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus
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