6 research outputs found
Screening drug candidates for sars-cov-2 spike protein variants within the SANCDB (South African Natural Compounds Database) and drug bank
No full textThe WHO declared the Coronavirus Infectious Disease 2019 (COVID-19) pandemic as over on the 5th of May 2023. However, the Severe Acute Respiratory Syndrome Coronavirus 2 Virus (SARS-CoV-2) is still prevalently spread within populations, causing hospitalization and death in serious infections. Most anti-COVID-19 agents are weakly or conditionally or even strongly recommended against in non-severe cases with low to medium risk of hospitalisation and further highlight the significance of effective treatments for SARS-CoV-2 infected patients. The host’s Angiotensin-Converting Enzyme 2 (ACE2) interaction with the viral spike protein’s Receptor-Binding Domain (RBD) of SARS-CoV-2 leads to the subsequent infection, viral replication, and further propagation of the virus. This establishes the spike protein’s RBD as a vital target for drug design. Through HADDOCK and AlphaFold driven structural refinement, the then novel SARS-CoV-2 delta [3.34 Å (PDB ID: 7WBQ)] and omicron [3.00 Å (PDB ID: 7WBP)] crystalline structures of the variants’ RBD, in complex with its host receptor human ACE2, were modelled to improve the low-resolution starting structures. Models predicted by HADDOCK independently yielded refined structures with improved resolutions of 2.49 Å (delta) and 2.41 Å (omicron). SARS-CoV-2 spike protein RBD of delta and omicron variants were screened for less frequently considered allosteric binding sites that could block ACE2-RBD engagement. Eight potential allosteric binding sites were identified through CavityPlus for both variants, with a single best druggable potential allosteric site identified for each. The search for potential inhibiting hit compounds involved using the SANCDB and DrugBank databanks and screening both the allosteric and orthosteric binding sites through molecular docking. Despite differences in mutated interacting residues and bond interactions, a lead compound for orthosteric binding sites (SANC00290) and potential allosteric modulators of both delta and omicron (SANC00746 and DB01029) were found. These compounds show promise in blocking ACE2-RBD engagement to potentially reduce viral interaction and infection of, and potentially withstanding further mutational residues. This study contributes to further investigation of affordable SA natural compound COVID-19 treatment and a starting point for in vitro analysis studies.Thesis (MSc) -- Faculty of Science, School of Biomolecular & Chemical Sciences, 202
Screening drug candidates for sars-cov-2 spike protein variants within the SANCDB (South African Natural Compounds Database) and drug bank
No full textThe WHO declared the Coronavirus Infectious Disease 2019 (COVID-19) pandemic as over on the 5th of May 2023. However, the Severe Acute Respiratory Syndrome Coronavirus 2 Virus (SARS-CoV-2) is still prevalently spread within populations, causing hospitalization and death in serious infections. Most anti-COVID-19 agents are weakly or conditionally or even strongly recommended against in non-severe cases with low to medium risk of hospitalisation and further highlight the significance of effective treatments for SARS-CoV-2 infected patients. The host’s Angiotensin-Converting Enzyme 2 (ACE2) interaction with the viral spike protein’s Receptor-Binding Domain (RBD) of SARS-CoV-2 leads to the subsequent infection, viral replication, and further propagation of the virus. This establishes the spike protein’s RBD as a vital target for drug design. Through HADDOCK and AlphaFold driven structural refinement, the then novel SARS-CoV-2 delta [3.34 Å (PDB ID: 7WBQ)] and omicron [3.00 Å (PDB ID: 7WBP)] crystalline structures of the variants’ RBD, in complex with its host receptor human ACE2, were modelled to improve the low-resolution starting structures. Models predicted by HADDOCK independently yielded refined structures with improved resolutions of 2.49 Å (delta) and 2.41 Å (omicron). SARS-CoV-2 spike protein RBD of delta and omicron variants were screened for less frequently considered allosteric binding sites that could block ACE2-RBD engagement. Eight potential allosteric binding sites were identified through CavityPlus for both variants, with a single best druggable potential allosteric site identified for each. The search for potential inhibiting hit compounds involved using the SANCDB and DrugBank databanks and screening both the allosteric and orthosteric binding sites through molecular docking. Despite differences in mutated interacting residues and bond interactions, a lead compound for orthosteric binding sites (SANC00290) and potential allosteric modulators of both delta and omicron (SANC00746 and DB01029) were found. These compounds show promise in blocking ACE2-RBD engagement to potentially reduce viral interaction and infection of, and potentially withstanding further mutational residues. This study contributes to further investigation of affordable SA natural compound COVID-19 treatment and a starting point for in vitro analysis studies.Thesis (MSc) -- Faculty of Science, School of Biomolecular & Chemical Sciences, 202
Nanofluidic qPCR unable to detect and serotype Streptococcus pneumoniae in urine samples of hospitalized South African patients with community-acquired pneumonia
No full textInternational audienceAbstract Pneumonia is a major cause of death among adults living with HIV in South Africa, but the etiology of many cases remains unknown. This study evaluated the utility of a nanofluidic qPCR assay to detect and serotype Streptococcus pneumoniae in urine samples from patients hospitalized with community-acquired pneumonia (CAP). The nanofluidic qPCR assay was optimized to target 13 pneumococcal serotypes and 4 reference genes. Archived urine samples collected from patients > 15 years of age hospitalized with pneumonia between April 2018 and August 2019 were retrospectively tested using the nanofluidic qPCR assay, BinaxNOW urine antigen test, and standard LytA qPCR. Blood culture was undertaken on a subset of the samples at the discretion of the attending physician. Cohens' Kappa statistics were used to determine the concordance between the methods. Of the 828 adults hospitalized for CAP, urine samples were available in 53% (n = 439). Of those, a random subset of 96 (22%) samples underwent testing. Of the participants included in the final analysis, the mean age was 45.8 years (SD 16.2), 49% (n = 47) were female, 98% (n = 94) were black, and 66% (n = 63) were living with HIV infection. The nanofluidic qPCR method was able to detect PCV13 vaccine strains spiked into urine samples; however, the method failed to detect any pneumococcus in clinical samples. In comparison, 19% of the pneumonia cases were attributed to S. pneumoniae using urine antigen testing. Nanofluidic qPCR is unable to detect and serotype Streptococcus pneumoniae in urine samples of South Africans hospitalized with CAP
Modelo de gestão da performance social orientada pelos stakeholders
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Engenharia de Produção.O objeto de estudo desta tese é a performance social das organizações. Parte-se do pressuposto que a medição e avaliação da performance requerem abordagens que capturem os efeitos resultantes das diferentes formas de relacionamentos e interações entre organizações e entidades do macroambiente. Tem-se como objetivo geral elaborar e avaliar um modelo de gestão da performance social sob a orientação dos stakeholders. Estudam-se os aspectos que definem e explicam as influências que os stakeholders exercem nas organizações a partir dos seus interesses e expectativas. A discussão é orientada por uma perspectiva normativa em que a performance é descrita como um compromisso moral das organizações e um construto social. A investigação foi desenvolvida com abordagem qualitativa, mediante um estudo de caso. Os dados utilizados resultam de levantamento documental e entrevistas individuais com stakeholders da empresa estudada. A análise de dados foi realizada com o uso de mapas cognitivos. A concepção do modelo de gestão apóia-se no referencial teórico nos dados documentais, resultando em quatro categorias explicativas: potencialidade-realidade das ações e proximidade-distância dos stakeholders. Os resultados da pesquisa, com a aplicação do modelo, mostram os direcionadores da performance social e como uma organização está sujeita ao comando de fora, quer pelos processos interativos com seus stakeholders, quer pelas interações entre os próprios stakeholders. Além da apresentação do modelo de gestão para a performance social, esta tese contribui para a validação empírica do conceito de stakeholder; para uma aproximação da Teoria dos Stakeholders com a Teoria Social; para o estabelecimento de procedimentos na análise de stakeholders, dentre outras
SARS-CoV-2 Viral Replication Persists in the Human Lung for Several Weeks after Symptom Onset
No full textInternational audienc
The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis
No full textThe ISOS study was funded through an unrestricted research
grant from Nestle Health Sciences. T.E.F.A. is supported by a
Medical Research Council/British Journal of Anaesthesia clinical
research training fellowship. B.B. is funded by a National
Research Foundation rating grant and an MRC (SA) selfinitiated
research grant. M.G. is a Chief Scientist Office (Scotland)
NHS Research Scheme Clinician. R.P. is a UK National
Institute for Health Research Professor
