One Year of Wastewater Surveillance in South Africa Supporting COVID-19 Clinical Findings Across Two Waves of Infection.

Wastewater-based epidemiology (WBE) has been an important tool for the detection of COVID-19 outbreaks. The retrospective analysis of COVID-19 data is vital to understand the spread and impact of the virus as well as to inform future planning and response efforts. In this study, we evaluated the SARS-CoV-2 RNA levels in wastewater from 21 wastewater treatment plants (WWTPs) in the City of Cape Town (South Africa) over a period of 12 months and compared the (inactive) SARS-CoV-2 viral RNA in wastewater between wave 2 (November 2020 to January 2021) and wave 3 (June 2021 to September 2021).

The Effect of Metformin and Hydrochlorothiazide on Cytochrome P450 3A4 Metabolism of Ivermectin: Insights from In Silico Experimentation.

The spread of SARS-CoV-2 has led to an interest in using ivermectin (a potent antiparasitic agent) as an antiviral agent despite the lack of convincing in vivo clinical data for its use against COVID-19. The off-target prophylactic use of ivermectin adds a substantial risk of drug-drug interactions with pharmaceutical medications used to treat chronic conditions like diabetes and hypertension (metformin and hydrochlorothiazide, respectively). Therefore, this study aims to evaluate the potential drug-drug interactions between ivermectin with either metformin or hydrochlorothiazide.

Evaluating the Therapeutic Potential of Curcumin and Synthetic Derivatives: A Computational Approach to Anti-Obesity Treatments.

Natural compounds such as curcumin, a polyphenolic compound derived from the rhizome of turmeric, have gathered remarkable scientific interest due to their diverse metabolic benefits including anti-obesity potential. However, curcumin faces challenges stemming from its unfavorable pharmacokinetic profile. To address this issue, synthetic curcumin derivatives aimed at enhancing the biological efficacy of curcumin have previously been developed.

Pancreatic beta cell regenerative potential of Zanthoxylum chalybeum Engl. Aqueous stem bark extract.

Ethnopharmacological Relevance: Zanthoxylum chalybeum Engl. is endemic to Africa and has been used traditionally to treat diabetes mellitus. Moreover, its pharmacological efficacy has been confirmed experimentally using in vitro and in vivo models of diabetes.

Dual-Target Inhibition: Insights into the Molecular Mechanism of Antifolate Drugs.

The escalating prevalence of drug-resistant strains of has posed a significant challenge to global efforts in combating tuberculosis. To address this issue, innovative therapeutic strategies are required that target essential biochemical pathways while minimizing the potential for resistance development. The concept of dual targeting has gained prominence in drug discovery against resistance bacteria.

Wastewater-based SARS-CoV-2 airport surveillance: key trends at the Cape Town International Airport.

Monitoring of SARS-CoV-2 RNA in wastewater has revealed the role of mobility in the transmission of coronavirus disease (COVID-19), and the surveillance of airport wastewater in cities across the world has demonstrated how travel entry points can give an indication of trends in transmission. This study undertook wastewater surveillance at the Cape Town International Airport (CTIA) to assess the use of a WBE approach to provide supplementary information on the presence of COVID-19 at a key air travel entry point in South Africa. Grab wastewater samples (n = 55) were collected from the CTIA wastewater pump station and analysed using quantitative real-time polymerase chain reaction (qRT-PCR) method.

(Honeybush) Induces Uncoupling Protein 1 and Peroxisome Proliferator-Activated Receptor Alpha Expression in Obese Diabetic Female db/db Mice.

Previously, we reported that a crude polyphenol-enriched fraction of (CPEF), a plant consumed as the herbal tea, commonly known as honeybush, reduced lipid content in 3T3-L1 adipocytes and inhibited body weight gain in obese, diabetic female leptin receptor-deficient (db/db) mice. In the current study, the mechanisms underlying decreased body weight gain in db/db mice were further elucidated using western blot analysis and in silico approaches. CPEF induced uncoupling protein 1 (UCP1, 3.

Using Wastewater Surveillance to Compare COVID-19 Outbreaks during the Easter Holidays over a 2-Year Period in Cape Town, South Africa.

Wastewater surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown to be an important approach to determine early outbreaks of infections. Wastewater-based epidemiology (WBE) is regarded as a complementary tool for monitoring SARS-CoV-2 trends in communities. In this study, the changes in the SARS-CoV-2 RNA levels in wastewater during Easter holidays in 2021 and 2022 in the City of Cape Town were monitored over nine weeks.

Delineating the Spread and Prevalence of SARS-CoV-2 Omicron Sublineages (BA.1-BA.5) and Deltacron Using Wastewater in the Western Cape, South Africa.

This study was one of the first to detect Omicron sublineages BA.4 and BA.5 in wastewater from South Africa.

Tracking the circulating SARS-CoV-2 variant of concern in South Africa using wastewater-based epidemiology.

This study uses wastewater-based epidemiology (WBE) to rapidly and, through targeted surveillance, track the geographical distribution of SARS-CoV-2 variants of concern (Alpha, Beta and Delta) within 24 wastewater treatment plants (WWTPs) in the Western Cape of South Africa. Information obtained was used to identify the circulating variant of concern (VOC) within a population and retrospectively trace when the predominant variant was introduced. Genotyping analysis of SARS-CoV-2 showed that 50% of wastewater samples harbored signature mutations linked to the Beta variant before the third wave, with the Delta variant absent within the population.

Spatial and Temporal Trends of SARS-CoV-2 RNA from Wastewater Treatment Plants over 6 Weeks in Cape Town, South Africa.

Recent scientific trends have revealed that the collection and analysis of data on the occurrence and fate of SARS-CoV-2 in wastewater may serve as an early warning system for COVID-19. In South Africa, the first COVID-19 epicenter emerged in the Western Cape Province. The City of Cape Town, located in the Western Cape Province, has approximately 4 million inhabitants.

Molecular dynamic mechanism(s) of inhibition of bioactive antiviral phytochemical compounds targeting cytochrome P450 3A4 and P-glycoprotein.

P-glycoprotein (ABCB1) and cytochrome P450 3A4 (CYP3A4) metabolize almost all known human immunodeficiency virus' protease inhibitor drugs (PIs). Over induction of these proteins' activities has been linked to rapid metabolism of PIs which are then pumped out of the circulatory system, eventually leading to drug-resistance in HIV-positive patients. This study aims to determine, with the use of computational tools, the inhibitory potential of four phytochemical compounds (PCs) (epigallocatechin gallate (EGCG), kaempferol-7-glucoside (K7G), luteolin (LUT) and ellagic acid (EGA)) in inhibiting the activities of these drug-metabolizing proteins.

Druggability and drug-likeness concepts in drug design: are biomodelling and predictive tools having their say?

The drug discovery process typically involves target identification and design of suitable drug molecules against these targets. Despite decades of experimental investigations in the drug discovery domain, about 96% overall failure rate has been recorded in drug development due to the "undruggability" of various identified disease targets, in addition to other challenges. Likewise, the high attrition rate of drug candidates in the drug discovery process has also become an enormous challenge for the pharmaceutical industry.

Delving into the Characteristic Features of "Menace" Mycobacterium tuberculosis Homologs: A Structural Dynamics and Proteomics Perspectives.

The global increase in the morbidity/mortality rate of Mycobacterial infections, predominantly renascent tuberculosis, leprosy, and Buruli ulcers have become worrisome over the years. More challenging is the incidence of resistance mediated by mutant Mycobacterium strains against front-line antitubercular drugs. Homologous to all Mycobacteria species is the GlcNAc-6-phosphate deacetylase (NagA) which catalyzes essential amino sugars synthesis required for cell wall architecture, hence, metamorphosing into an important pharmacological target for curtailing virulence and drug-resistance.

The Dual-Targeting Activity of the Metabolite Substrate of Para-amino Salicyclic Acid in the Mycobacterial Folate Pathway: Atomistic and Structural Perspectives.

Therapeutic targeting of folate biosynthetic pathway has recently been explored as a viable strategy in the treatment of tuberculosis. The bioactive metabolite substrate of Para-amino salicyclic acid (PAS-M) reportedly dual-targets dihydrofolate reductase (DHFR) and flavin-dependent thymidylate synthase (FDTS), two essential enzymes in folate biosynthetic pathway. However, the molecular mechanisms and structural dynamics of this dual inhibitory activity of the PAS-M remain elusive.

Human Rhinovirus Inhibition Through Capsid "Canyon" Perturbation: Structural Insights into The Role of a Novel Benzothiophene Derivative.

The challenge in targeting human rhinoviruses (HRV) over the years has been attributed to the wide variety in HRV serotypes. Nonetheless, the search for therapeutic agents against HRV continues unabated. These efforts have been augmented by the recent discovery of the novel benzothiophene derivative shown to inhibit HRV viral replication.

The pharmacokinetic properties of HIV-1 protease inhibitors: A computational perspective on herbal phytochemicals.

Acquired Immune Deficiency Syndrome is the most severe phase of Human Immunodeficiency Virus (HIV) infection. Recent studies have seen an effort to isolate phytochemicals from plants to repress HIV, but less studies have focused on the effects of these phytochemicals on the activities of enzymes/transporters involved in the metabolism of these drugs, which is one of the aims of this study and, to examine the antiviral activity of these compounds against HIV-1 protease enzyme using computational tools. Centre of Awareness-Food Supplement (COA®-FS) herbal medicine, has been said to have potential anti-HIV features.

Tracing Potential Covalent Inhibitors of an E3 Ubiquitin Ligase through Target-Focused Modelling.

The Nedd4-1 E3 Ubiquitin ligase has been implicated in multiple disease conditions due its overexpression. Although the enzyme may be targeted both covalently and non-covalently, minimal studies provide effective inhibitors against it. Recently, research has focused on covalent inhibitors based on their characteristic, highly-selective warheads and ability to prevent drug resistance.

Discovery of novel natural flavonoids as potent antiviral candidates against hepatitis C virus NS5B polymerase.

The non-structural 5B (NS5B) polymerase of hepatitis C virus (HCV) is an attractive target for antiviral intervention. Quercetagetin (Que) is a natural flavonoid, which has been exhibited to have anti-HCV property through inhibition of RNA binding to NS5B. The last few decades have witnessed a growing interest in the extraction of natural flavonoids with a plethora of different biological activities.

Navigating Research Toward the Re-emerging Nipah Virus- A New Piece to the Puzzle.

Background: The recent Nipah virus (NiV) outbreak in India has caused a state of chaos, with potential to become the next international pandemic. There is still a great deal to learn about NiV for the development of a potent treatment against it. The NiV non-structural proteins play important roles in the lifecycle of the virus, with the RNA-dependent RNA-polymerase (RdRp) being a vital component in viral replication.

The Perplexity of Synergistic Duality: Inter-molecular Mechanisms of Communication in BCR-ABL1.

Background: Aberrant and proliferative expression of the oncogene BCR-ABL in bone marrow cells is one of the prime causes of Chronic Myeloid Leukemia (CML). It has been established that the tyrosine kinase domain of the BCR-ABL protein is a potential therapeutic target for the treatment of CML. Although the first and second line inhibitors against the enzyme are available, recent studies have indicated that monotherapeutic resistance has become a great challenge.

Grafted hyaluronic acid N-acetyl-l-methionine for targeting of LAT1 receptor: In-silico, synthesis and microscale thermophoresis studies.

Neutral amino acids can be delivered into cells through the l-type amino acid transporter-1 (LAT1), which is a sodium independent transporter. The LAT1 protein is expressed in different tissues, including kidney, blood brain barrier and intestinal wall hence LAT1 can be used as a target in diseases associated with its overexpression. In-silico interactions between different ligands, including methionine (Met), N-acetyl-l-methionine (AcMet), hyaluronic acid (HA), grafted hyaluronic-acid l-methionine (HA-ADH-Met) and a novel grafted hyaluronic acid-N-acetyl-l-methionine (HA-ADH-AcMet), which are at the active site of the LAT1 transporter, were studied and the binding energies calculated.

Allosteric inhibition induces an open WPD-loop: a new avenue towards glioblastoma therapy.

The mobility of loops around the catalytic site of a protein remains crucial to its activity. Dynamics of the WPD-loop is an essential determinant of the catalytic activity of tyrosine-protein phosphatase zeta, an implicated protein in glioblastoma cells. The WPD-loop assumes a closed conformation upon substrate binding in order to position its catalytic aspartate to participate in catalysis.

Domperidone nanocrystals with boosted oral bioavailability: fabrication, evaluation and molecular insight into the polymer-domperidone nanocrystal interaction.

The aim of this study was to employ experimental and molecular modelling approaches to use molecular level interactions to rationalise the selection of suitable polymers for use in the production of stable domperidone (DOMP) nanocrystals with enhanced bioavailability. A low-energy antisolvent precipitation method was used for the preparation and screening of polymers for stable nanocrystals of DOMP. Ethyl cellulose was found to be very efficient in producing stable DOMP nanocrystals with particle size of 130 ± 3 nm.