Papers by Kirabo Tess Ayazika
bioRxiv (Cold Spring Harbor Laboratory), Apr 20, 2021
Identification of druggable host targets needed for SARS-CoV-2 infection by combined pharmacologi... more Identification of druggable host targets needed for SARS-CoV-2 infection by combined pharmacological evaluation and cellular network directed prioritization both in vitro and in vivo.
iScience, Sep 1, 2022
Pharmacologically active compounds with known biological targets were evaluated for inhibition of... more Pharmacologically active compounds with known biological targets were evaluated for inhibition of SARS-CoV-2 infection in cell and tissue models to help identify potent classes of active small molecules and to better understand host-virus interactions. We evaluated 6,710 clinical and preclinical compounds targeting 2,183 host proteins by immunocytofluorescence-based screening to identify SARS-CoV-2 infection inhibitors. Computationally integrating relationships between small molecule structure, dose-response antiviral activity, host target, and cell interactome produced cellular networks important for infection. This analysis revealed 389 small molecules with micromolar to low nanomolar activities, representing >12 scaffold classes and 813 host targets. Representatives were evaluated for mechanism of action in stable and primary human cell models with SARS-CoV-2 variants and MERS-CoV. One promising candidate, obatoclax, significantly reduced SARS-CoV-2 viral lung load in mice. Ultimately, this work establishes a rigorous approach for future pharmacological and computational identification of host factor dependencies and treatments for viral diseases.
PLOS ONE, May 7, 2021
Introduction Proper measures to combat antimicrobial resistance development and spread in Sub Sah... more Introduction Proper measures to combat antimicrobial resistance development and spread in Sub Saharan Africa are very crucial bearing in mind the projected burden of antimicrobial resistance which is expected to be increase by 2050. Training of medical doctor and pharmacy students in antimicrobial stewardship is vital to combat antimicrobial resistance. This study was designed to evaluate the knowledge, attitude, and perception of final year medical and pharmacy students on antimicrobial use and antimicrobial resistance at three universities in Uganda, Kenya, and Tanzania. Methodology A cross-sectional survey was carried out among final year undergraduate medical and pharmacy students at three universities in East Africa. A Self-administered questionnaire was developed which included dichotomous questions and questions using a 4-point Likert scale. The questions were based on knowledge and attitude about antibiotics, and preparedness to use antibiotics in clinical scenarios. Data were analyzed using STATA version 16 following the objective of the study. Results Three hundred and twenty-eight final year students participated in the survey from MUK 75, MKU 75 and CUHAS 178. Slightly majority of participants were male 192(58.5%) and their median age was 25 [23-27] years. In general, 36.6% (120/328) of students had good overall total knowledge. More students at MUK had good knowledge compared to MKU, and
Advances in Medical Education and Practice, 2021
Introduction: Contaminated mobile phones act as reservoirs for organisms causing hospital-acquire... more Introduction: Contaminated mobile phones act as reservoirs for organisms causing hospital-acquired infections (HAI). Little is known about medical school students' awareness of infection prevention and control (IPC) regarding mobile phone use among medical students. We demonstrated the presence of organisms on mobile phones of final-year medical students at Makerere University College of Health Sciences and evaluated their awareness of IPC regarding mobile phone hygiene and use in a hospital setting. Methods: In this cross-sectional study, organisms from swabs obtained from 79 medical students' mobile phones were identified and antimicrobial susceptibility test carried out using standard biochemical tests and the automated BD Phoenix instrument. Data were collected using a self-administered questionnaire to assess the students' awareness. The analysis was carried out using STATA software version 16. Results: Seventy (88.6%) mobile phones were contaminated with at least one organism. One hundred forty-eight bacteria were isolated, of which 123 (83.1%) were Gram-positive, 24 (16.2%) were Gram-negative, and 1 (0.7%) was yeast (Candida spp). Coagulase negative staphylococci were the most frequently isolated among Gram-positive bacteria. Acinetobacter baumannii were the most frequently isolated among Gram-negative bacteria. The average IPC practical score regarding mobile phone hygiene (34%) was significantly lower than the average IPC awareness score (77%) (p ≤ 0.0001). Seventy-four (93.7%) students use their phones while rotating in the various wards. Forty (50.6%) of the students cleaned their phones with alcohol-based sanitizer after rotations in the ward. Thirty-five (44.3%) students were aware of IPC programs in the hospital they rotated in. Conclusion: There is a high prevalence of bacterial contamination from mobile phones of medical students. The students had lower IPC practical scores compared to IPC awareness scores regarding mobile phone hygiene irrespective of the ward of rotation. Curriculum of final-year medical students should include IPC-related topics, which incorporate practical skills.
PLOS ONE, 2021
Introduction Proper measures to combat antimicrobial resistance development and spread in Sub Sah... more Introduction Proper measures to combat antimicrobial resistance development and spread in Sub Saharan Africa are very crucial bearing in mind the projected burden of antimicrobial resistance which is expected to be increase by 2050. Training of medical doctor and pharmacy students in antimicrobial stewardship is vital to combat antimicrobial resistance. This study was designed to evaluate the knowledge, attitude, and perception of final year medical and pharmacy students on antimicrobial use and antimicrobial resistance at three universities in Uganda, Kenya, and Tanzania. Methodology A cross-sectional survey was carried out among final year undergraduate medical and pharmacy students at three universities in East Africa. A Self-administered questionnaire was developed which included dichotomous questions and questions using a 4-point Likert scale. The questions were based on knowledge and attitude about antibiotics, and preparedness to use antibiotics in clinical scenarios. Data we...
Identification of host factors contributing to replication of viruses and resulting disease progr... more Identification of host factors contributing to replication of viruses and resulting disease progression remains a promising approach for development of new therapeutics. Here, we evaluated 6710 clinical and preclinical compounds targeting 2183 host proteins by immunocytofluorescence-based screening to identify SARS-CoV-2 infection inhibitors. Computationally integrating relationships between small molecule structure, dose-response antiviral activity, host target and cell interactome networking produced cellular networks important for infection. This analysis revealed 389 small molecules, >12 scaffold classes and 813 host targets with micromolar to low nanomolar activities. From these classes, representatives were extensively evaluated for mechanism of action in stable and primary human cell models, and additionally against Beta and Delta SARS-CoV-2 variants and MERS-CoV. One promising candidate, obatoclax, significantly reduced SARS-CoV-2 viral lung load in mice. Ultimately, this...
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Papers by Kirabo Tess Ayazika