Browsing by Author "Vuai, Said"

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Abrogating the nsp10–nsp16 switching mechanisms in SARS-CoV-2 by phytochemicals from Withania somnifera: a molecular dynamics study
(Taylor & Francis Online, 2021-09-14) Vuai, Said; Onoka, Isaac; Sahini, Mtabazi; Swai, Hulda; Shadrack, Daniel
The search for therapeutic small molecules and vaccines for Covid-19 treatment is an urgent but evolving topic. The virus has claimed over 3,782,490 lives (as of 12 June 2021), with the figure expected to rise due to the high versatility of the SAR-CoV-2 variant. Therapeutic options based on SARS-CoV-2 inhibitor are essential. Withanolides have a long history in traditional medicines with versatile biological properties including antiviral activities. In this study, the inhibitory potential of withanolides from Withania somnifera (Ashwagandha) against SARS-CoV-2 non-structural protein 10 (nsp10) was investigated by employing atomistic in silico methods viz molecular docking, molecular dynamics and binding free energy calculations. Investigated Withania somnifera compounds demonstrated binding affinity to the nsp10 and in its complex form, that is, nsp10-nsp16 heterodimer. Two withanolides; withanoside IV and withanoside V isolated from the roots of Withania somnifera demonstrated strong inhibition with binding free energies of −29.5 and −29.1 kJ/mol, respectively. Molecular dynamics and binding free energy ascertained the stability of withanoside IV. Water molecules, although known to play an important role in mediating biological systems, herein, water was found to have a repulsive binding effect to some residues, suggesting that the binding of withanoside IV would require dewetting of the nsp10 or displacing the water to bulk solvents. Interestingly, residues in the nsp10 that are responsible for forming stable interaction at the nsp10–nsp16 were found to be strongly interacting with withanoside IV, hence weakening the nsp10–nsp16 interaction and recognition. Further in vitro and in vivo experiments are recommended to validate the anti-SARS-COV-2 potential of these phytochemicals.
Antibiotic-resistant microbial populations in urban receiving waters and wastewaters from Tanzania
(Elsevier, 2023) Ripanda, Asha; Rwiza, Mwemezi; Nyanza, Elias; Miraji, Hossein; Bih, Numfor; Mzula, Alexanda; Mwega, Elisa; Njau, Karoli; Vuai, Said; Machunda, Revocatus
Antimicrobial resistance against certain medications in the pathogenic microbial community is globally increasing due to the continual discharge and disposal of pharmaceuticals in the environment. The phenomenon resulted in significant antibiotic resistance among several exposed Enterobacteriaceae species, with wastewater treatment plants (WWTPs) and rivers serving as significant reservoirs. Despite antibiotic resistance being a tragedy, particularly in treating diseases by using antibiotics, local and regional studies indicating the severity, resistant species and the molecular level insight into these pathogens are scarce, thus requiring immediate intervention. This study, therefore, investigated wastewater from wastewater treatment ponds and receiving waters for the presence of resistant pathogens through phenotypical and molecular approach screening of their genes. Among the 57 analyzed samples, 18 (67%, n = 27) isolates of Klebsiella spp.., 4 (80%, n = 5) isolates of Proteus spp., 1 (100%, n = 1) of isolated Pseudomonas aeruginosa and 6 (18%, n = 34) of E. coli found were resistant to at least 1 among the tested antibiotics. E. coli had an 83% higher proportion of multi-drug resistance (MDR) than Klebsiella spp.., which had 68.5%, and no MDR was shown by P. aeruginosa isolates. Among the 20 bacterial isolates of antibiotic-resistant genes, showed that E. coli harboured 39%, followed by 22% of Klebsiella spp. Eleven (11) isolates of these 20 (55%) contained sulphonamides resistant genes: Sul 1 (n = 4) and Sul 2 (n = 7). Ten (10) isolates (50%) contained the tetracycline-resistant genes in which 4 isolates showed the Tet A, Tet B – 1 and 5 isolates contained Tet D. β-lactamases (bla CTX-M and bla SHV) were found in 7 isolates (35%). The existence of these antibiotic-resistant species in the urban receiving and wastewater presents a threat of transmission of diseases to humans and animals that are not cured by the existing medications, jeopardizing public health safety.
Combatting toxic chemical elements pollution for Sub-Saharan Africa's ecological health
(Elsevier, 2025-02-08) Ripanda, Asha; Hossein, Miraji; Rwiza, Mwemezi; Nyanza, Elias; Selemani, Juma; Nkrumah, Salma; Bakari, Ramadhani; Alfred, Mateso; Machunda, Revocatus; Vuai, Said
With its booming mining, processing industries, agriculture, and increasing urbanization, sub-Saharan Africa experiences an alarming rise in accumulation of toxic chemical elements in all environmental matrices threatening entire ecology. Most toxic chemical elements are mercury, lead, cadmium, chromium, and arsenic. These toxic chemical elements are known human carcinogens, systemic toxicants and can induce multiple organ damage. The occurrences of toxic chemical elements in Sub-Saharan Africa are amplified by anthropogenic activities such as mining, industrial discharges, and agricultural practices. This study examined the extent of exposure to toxic chemical elements in surface and underground waters, sediments, soils, effluents, food crops, vegetables, aquatic organisms, industrial products, humans, and other animals in Sub-Saharan Africa. Results indicate occurrences of toxic chemical elements in surface and underground waters, sediments, soils, effluents, food crops, vegetables, aquatic organisms, industrial products, humans, and other animals above the recommended threshold. These findings highlight the persistent pollution of water, soil, sediments, food crops, aquatic organisms, and even industrial products, emphasizing the potential for bioaccumulation and exposure through the food chain. This requires interdisciplinary approaches, including updating and enforcing stricter regulations tailored to regional industrial and agricultural practices. Advanced remediation technologies, such as phytoremediation, and bioremediation, should be prioritized to remove toxic chemical elements from affected environments. Additionally, promoting sustainable practices, such as waste recycling programs, can help reduce anthropogenic contributions, strengthen environmental monitoring systems, nurture community awareness, and essentially encourage regional and international collaboration to protect ecosystems and safeguard human health in Sub-Saharan Africa.
Contribution of Illicit Drug Use to Pharmaceutical Load in the Environment: A Focus on Sub-Saharan Africa
(Hindawi, 2022-07-08) Ripanda, Asha; Rwiza, Mwemezi; Nyanza, Elias; Machunda, Revocatus; Vuai, Said
Illicit drug abuse and addiction are universal issues requiring international cooperation and interdisciplinary and multisectoral solutions. ese addictive substances are utilized for recreational purposes worldwide, including in sub-Saharan Africa. On the other hand, conventional wastewater treatment facilities such as waste stabilization ponds lack the design to remove the most recent classes of pollutants such as illicit drug abuse. As a result, e uents from these treatment schemes contaminate the entire ecosystem. Public health o cials are concerned about detecting these pollutants at alarming levels in some countries, with potential undesirable e ects on aquatic species and increased health hazards through exposure to contaminated waters or recycling treated or untreated e uents in agriculture. Contaminants including illicit substances enter the environment by human excreta following illegal intake, spills, or through direct dumping, such as from clandestine laboratories, when their manufacturer does not follow accepted production processes. ese substances, like other pharmaceuticals, have biological activity and range from pseudopersistent to highly persistent compounds; hence, they persist in the environment while causing harm to the ecosystem. e presence of powerful pharmacological agents such as cocaine, morphine, and amphetamine in water as complex combinations can impair aquatic organisms and human health. ese compounds can harm human beings and ecosystem health apart from their low environmental levels. erefore, this article examines the presence and levels of illicit substances in ecological compartments such as wastewater, surface and ground waters in sub-Saharan Africa, and their latent impact on the ecosystem. e information on the occurrences of illicit drugs and their metabolic products in the sub-Saharan Africa environment and their contribution to pharmaceutical load is missing. In this case, it is important to research further the presence, levels, distribution, and environmental risks of exposure to human beings and the entire ecosystem.
Data from the batch adsorption of ciprofloxacin and lamivudine from synthetic solution using jamun seed (Syzygium cumini) biochar: Response surface methodology (RSM) optimization
(Elsevier, 2023-02) Ripanda, Asha; Rwiza, Mwemezi; Nyanza, Elias; Bakari, Ramadhani; Miraji, Hossein; Njau, Karoli; Vuai, Said; Machunda, Revocatus
This dataset expresses the experimental data on the batch adsorption of ciprofloxacin and lamivudine from synthetic solution using jamun seed (JS) (Syzygium cumini) biochar. Independent variables including concentration of pollutants (10-500 ppm), contact time (30–300 min), adsorbent dosage (1-1000 mg), pH (1-14) and adsorbent calcination temperature (250,300, 600 and 750 °C) were studied and optimized using Response Surface Methodology (RSM). Empirical models were developed to predict the maximum removal efficiency of ciprofloxacin and lamivudine, and the results were compared with the experimental data. The removal of polutants was more influenced by concentration, followed by adsorbent dosagage, pH, and contact time and the maximum removal reached 90%.
Ecological Consequences of Antibiotics Pollution in Sub-Saharan Africa: Understanding Sources, Pathways, and Potential Implications
(KeAi, 2025-01-25) Ripanda, Asha; Rwiza, Mwemezi; Nyanza, Elias; Hossein, Miraji; Alfred, Mateso; Mahmoud, Alaa; Murthy, Ananda; Bakari, Ramadhani; Vuai, Said; Machunda, Revocatus
In Sub-Saharan Africa (SSA), the increasing use of antibiotics in human and veterinary medicine, combined with inadequate waste and water management systems, has intensified the problem of antibiotic pollution. Untreated or partially treated wastewater from industries, agricultural runoff, residential areas, and healthcare facilities is frequently discharged into the environment, often used for irrigation, contributing to antibiotic accumulation, the spread of resistance genes, and the rise of antibiotic resistance, posing serious threats to public health and environmental sustainability. The region's climatic conditions favour the survival and proliferation of microbial communities, including pathogens. Additionally, the high prevalence of infectious diseases such as HIV/AIDS, tuberculosis, and malaria, which often necessitate antibiotic use, further amplifies the issue. Systemic challenges, including poor waste management, inadequate or absent wastewater treatment infrastructure, weak regulatory enforcement, and the over-the-counter sale of antibiotics, exacerbate the crisis. Limited healthcare access often results in self-medication and improper antibiotic use, accelerating resistance spread. Evidence shows antibiotics in surface water, groundwater, effluents, food crops, environmental samples, and aquatic organisms, indicating their potential circulation through the food chain. However, a lack of comprehensive data on antibiotic pollution and its impacts on aquatic ecosystems in SSA hampers a thorough understanding of its scope and long-term effects. Addressing this crisis requires identifying contamination hotspots, evaluating ecological impacts, and establishing robust, region-specific regulatory frameworks to ensure environmental and public health safety
Relaxed complex scheme and molecular dynamics simulation suggests small molecule inhibitor of human TMPRSS2 for combating COVID-19
(Taylor & Francis online, 2021-11-09) Vuai, Said; Ogedjo, Marcelina; Onoka, Isaac; Sahini, Mtabazi; Swai, Hulda; Shadrack, Daniel
As the coronavirus disease 19 (COVID-19) pandemic continues to pose a health and economic crisis worldwide, the quest for drugs and/or vaccines against the virus continues. The human transmembrane protease serine 2 (TMPRSS2) has attracted attention as a target for drug discovery, as inhibition of its catalytic reaction would result in the inactivation of the proteolytic cleavage of the SARS-CoV-2 S protein. As a result, the inactivation prevents viral cell entry to the host’s cell. In this work, we screened and identified two potent molecules that interact and inhibit the catalytic reaction by using computational approaches. Two docking screening experiments were performed utilizing the crystal structure and holo ensemble structure obtained from molecular dynamics in bound form. There is enhancement and sensitivity of docking results to the holo ensemble as compared to the crystal structure. Compound 1 demonstrated a similar inhibition value to nafamostat by interacting with catalytic triad residues His296 and Ser441, thereby disrupting the already established hydrogen bond interaction. The stability of the ligand–TMPRSS2 complexes was studied by molecular dynamics simulation, and the binding energy was re-scored by using molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy. The obtained compounds may serve as an initial point toward the discovery of potent TMPRSS2 inhibitors upon further in vivo validation.
Removal of lamivudine from synthetic solution using jamun seed (Syzygium cumini) biochar adsorbent
(Emerging Contaminants, 2023-09-01) Ripanda, Asha; Rwiza, Mwemezi; Nyanza, Elias; Bakari, Ramadhani; Bakari, Ramadhani; Miraji, Hossein; Njau, Karoli; Vuai, Said; Machunda, Revocatus
Antiviral drugs such as lamivudine have been globally identified in the environment and marked as emerging pollutants of concern due to their bioactive extremity. Following therapeutic uses, approximately 70% of the oral dose of lamivudine is eliminated renally as the parent drug. Concerns has been raised for neighbouring aquatic bodies due to effluent produced from production plants containing high concentrations of antiviral drugs. Antiviral drugs, such as lamivudine, are extremely bioactive, prompting interest in their urgent removal from the environment. The purpose of the present study was to optimize the removal of lamivudine from the synthetic solution using jamun seed (JS) (Syzygium cumini) biochar. The influence of sorption parameters such as pH, lamivudine concentration, adsorbent dosage, contact time, and calcination temperatures on the removal of lamivudine was investigated and optimized using a response surface methodology (SRM) based on optimal design. The results indicated that, a quadratic model best fits data with a model regression coefficient R2, adjusted R2, and predicted R2 of 0.9934, 0.9761 and 0.8340, respectively. The JS biochar calcined at 750 °C, at pH 8, initial lamivudine concentration of 10 ppm and contact time of 30 min indicated a maximum experimental removal efficiency of 84.9%. The residual standard error (RSE) value was 3.5% implying that the model was reliable. Isotherm data for the adsorption of lamivudine on JS biochar followed the Freundlich isotherm, with an R2 value of 0.9977 while R2 for the modified Langmuir model was 0.9852. These findings indicated that JS biochar is potentially useful for removal of lamivudine, and other organics from contaminated water and wastewater effluents. Therefore, this study presents an environmentally friendly remedy against lamivudine for a healthier ecology.
A Review on Contaminants of Emerging Concern in the Environment: A Focus on Active Chemicals in Sub-Saharan Africa
(MDPI, 2021-12-22) Ripanda, Asha; Rwiza, Mwemezi; Nyanza, Elias; Njau, Karoli; Vuai, Said; Machunda, Revocatus
: Active chemicals are among the contaminants of emerging concern that are rarely covered in regulatory documents in sub-Saharan Africa. These substances are neither in the list of routinely monitored substances nor in the guidelines for routine environmental monitoring activities. This has been of concern to public health officials, toxicologists, communities, and governments, hence the need for risk assessment and regulation of these substances. In this review article, the presence of active chemicals in the sub-Saharan African environment was investigated. The results indicate the availability of few studies in some countries, while in other countries no reports of active chemicals were found, hence the need for further research targeting such countries. It was further observed that mixtures of active chemicals from different therapeutic categories—such as antibiotics and analgesics—were reported. The natural environment is increasingly at risk due to the presence of these substances, their metabolites, and their transformation byproducts. These substances are characterized by persistence as a result of their non-biodegradable nature; hence, they circulate from one environmental compartment to another through the food chain, causing harm along the way. Most studies that evaluated the toxicity of these substances considered the effects of a single drug, but observations indicated the presence of drug mixtures, hence the need for further evaluation of the effects of drug–drug interactions—including synergistic and additive effects—for environmental sustainability. The presence of ACs in several environmental compartments at quantifiable quantities was discovered in this investigation, indicating the potential for ecosystem injury as a result of bioaccumulation, bioconcentration, and biomagnification through the food chain. This necessitates further research on the subject in order to ensure a healthier environment.