Research Articles (SANBI)http://hdl.handle.net/10566/7982024-03-28T15:29:42Z2024-03-28T15:29:42ZUnveiling the inhibitory potentials of peptidomimetic azanitriles and pyridyl esters towards sars-cov-2 main protease: a molecular modelling investigationOdugbemi, Adeshina I.Mushebenge, Aganze G.Ugbaja, Samuel Chttp://hdl.handle.net/10566/93122024-02-16T00:00:40Z2023-01-01T00:00:00ZUnveiling the inhibitory potentials of peptidomimetic azanitriles and pyridyl esters towards sars-cov-2 main protease: a molecular modelling investigation
Odugbemi, Adeshina I.; Mushebenge, Aganze G.; Ugbaja, Samuel C
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for COVID-19, which was declared a global pandemic in March 2020 by the World Health Organization (WHO). Since SARS-CoV-2 main protease plays an essential role in the virus’s life cycle, the design of small drug molecules with lower molecular weight has been a promising development targeting its inhibition. Herein, we evaluated the novel peptidomimetic azatripeptide and azatetrapeptide nitriles against SARS-CoV-2 main protease. We employed molecular dynamics (MD) simulations to elucidate the selected compounds’ binding free energy profiles against SARS-CoV-2 and further unveil the residues responsible for the drug-binding properties. Compound 8 exhibited the highest binding free energy of −49.37 ± 0.15 kcal/mol, followed by compound 7 (−39.83 ± 0.19 kcal/mol), while compound 17 showed the lowest binding free energy (−23.54 ± 0.19 kcal/mol). In addition, the absorption, distribution, metabolism, and excretion (ADME) assessment was performed and revealed that only compound 17 met the drug-likeness parameters and exhibited high pharmacokinetics to inhibit CYP1A2, CYP2C19, and CYP2C9 with better absorption potential and blood-brain barrier permeability (BBB) index. The additional intermolecular evaluations suggested compound 8 as a promising drug candidate for inhibiting SARS-CoV-2 Mpro. The substitution of isopropane in compound 7 with an aromatic benzene ring in compound 8 significantly enhanced the drug’s ability to bind better at the active site of the SARS-CoV-2 Mpro.
2023-01-01T00:00:00ZCovid-19 among adults living with HIV: Correlates of mortality among public sector healthcare users in Western Cape, South AfricaKassanjee, ReshmaDavies, Mary-AnnTiffin, Nickihttp://hdl.handle.net/10566/92082023-07-18T00:00:50Z2023-01-01T00:00:00ZCovid-19 among adults living with HIV: Correlates of mortality among public sector healthcare users in Western Cape, South Africa
Kassanjee, Reshma; Davies, Mary-Ann; Tiffin, Nicki
Introduction: While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty
about the role of HIV disease severity on COVID-19 outcomes, especially in lower-income settings. We studied the
association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH.
Methods: We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS-CoV-2 infection
(until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression
was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV
evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID-19 vaccination, adjusting for
demographic characteristics, comorbidities, admission pressure, location and time period.
Results: Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first-diagnosed infections. Higher mortality was associated
with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence,
differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more
recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality,
more strongly in younger adults.
2023-01-01T00:00:00ZRecord linkage for routinely collected health data in an African health information exchangeMutemaringa, ThembaHeekes, AlexaTiffin, Nickihttp://hdl.handle.net/10566/91272023-06-22T00:00:50Z2023-01-01T00:00:00ZRecord linkage for routinely collected health data in an African health information exchange
Mutemaringa, Themba; Heekes, Alexa; Tiffin, Nicki
The Patient Master Index (PMI) plays an important role in management of patient information and
epidemiological research, and the availability of unique patient identifiers improves the accuracy when
linking patient records across disparate datasets. In our environment, however, a unique identifier is
seldom present in all datasets containing patient information. Quasi identifiers are used to attempt to
link patient records but sometimes present higher risk of over-linking. Data quality and completeness
thus affect the ability to make correct linkages. This paper describes the record linkage system that is currently implemented at the Provincial Health
Data Centre (PHDC) in the Western Cape, South Africa, and assesses its output to date.
2023-01-01T00:00:00ZApplication of an in silico approach identifies a genetic locus within ITGB2, and its interactions with HSPG2 and FGF9, to be associated with anterior cruciate ligament rupture riskDlamini, Senanile B.Saunders, Colleen J.Laguette, Mary-Jessica N.http://hdl.handle.net/10566/90732023-06-14T00:00:58Z2023-01-01T00:00:00ZApplication of an in silico approach identifies a genetic locus within ITGB2, and its interactions with HSPG2 and FGF9, to be associated with anterior cruciate ligament rupture risk
Dlamini, Senanile B.; Saunders, Colleen J.; Laguette, Mary-Jessica N.
We developed a Biomedical Knowledge Graph model that is phenotype and biological functionaware
through integrating knowledge from multiple domains in a Neo4j, graph database. All
known human genes were assessed through the model to identify potential new risk genes for
anterior cruciate ligament (ACL) ruptures and Achilles tendinopathy (AT). Genes were prioritised
and explored in a case–control study comparing participants with ACL ruptures (ACL-R),
including a sub-group with non-contact mechanism injuries (ACL-NON), to uninjured control
individuals (CON). After gene filtering, 3376 genes, including 411 genes identified through
previous whole exome sequencing, were found to be potentially linked to AT and ACL ruptures.
Four variants were prioritised: HSPG2:rs2291826A/G, HSPG2:rs2291827G/A, ITGB2:rs2230528C/T
and FGF9:rs2274296C/T. The rs2230528 CC genotype was over-represented in the CON group
compared to ACL-R (p < 0.001) and ACL-NON (p < 0.001) and the TT genotype and T allele were
over-represented in the ACL-R group and ACL-NON compared to CON (p < 0.001) group.
2023-01-01T00:00:00Z