Department of Biochemistry & Molecular Biology

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    Design of a multi-epitope vaccine against drug-resistant mycobacterium tuberculosis and mycobacterium bovis using reverse vaccinology
    (Nature, 2025) Akurut, Eva; Gavamukulya, Yahaya; Mulindwa, Julius; Isiagi, Moses; Galiwango, Ronald; Bbuye, Mudarshiru; Lujumba, Ibra; Kiberu, Davis; Nabisubi, Patricia; Kebirungi, Grace; Kambugu, Andrew; Castelnuovo, Barbara; Nkurunungi, Gyaviira; Jjingo, Daudi; Oketch, Brenda; Kateete, David Patrick; Mboowa, Gerald
    The global burden of Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium bovis (M. bovis), the rise of drug-resistant strains, necessitates an urgent need for developing more effective vaccines. This study employed an in-silico approach to design a multi-epitope vaccine targeting the PE_PGRS16 protein, a conserved virulence factor found across both species, including drug-resistant strains. PE_PGRS16 was chosen due to its extracellular localization, adhesion properties, and virulence characteristics, making it a promising vaccine target. Epitopes for B-cells, Cytotoxic T Lymphocytes, and Helper T Lymphocytes were selected based on antigenicity, non-toxicity, and immune response potential. The vaccine construct demonstrated favorable properties, including high antigenicity, solubility, and stability, with a low instability index (-31.31) and binding energy (-44.566) when docked to TLR4, suggesting its potential for immune activation. Griselimycin was incorporated as an adjuvant to enhance immunogenicity, as predicted by C-ImmSim simulations. Population coverage analysis for East Africa revealed high applicability, with 98.35% coverage for Class I epitopes, 100% coverage for Class II epitopes, and 100% combined coverage, with average hit values of 8.4, 12.26, and 20.66, respectively. These results suggest broad potential for global vaccine deployment. This study presents a novel multi-epitope vaccine targeting PE_PGRS16, with the potential to combat Mycobacterium tuberculosis and Mycobacterium bovis infections, including drug-resistant forms. Further experimental validation is necessary to confirm its efficacy and safety. Keywords Mycobacterium tuberculosis, Mycobacterium bovis, Vaccines, BCG, Reverse vaccinology, Molecular Docking, Tuberculosis, Drug resistance
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    Annona muricata silver nanoparticles exhibit strong anticancer activities against cervical and prostate adenocarcinomas through regulation of CASP9 and the CXCL1/CXCR2 genes axis
    (IOS Press, 2021) Gavamukulya, Yahaya; Mainab, Esther N.; El-Shemy, Hany A.; Merokac, Amos M.; Kangogo, Geoffrey K.; Magomab, Gabriel; Wamunyokoli, Fred
    BACKGROUND: Green synthesized nanoparticles have been earmarked for use in nanomedicine including for the development of better anticancer drugs. OBJECTIVE: The aim of this study was to undertake biochemical evaluation of anticancer activities of green synthesized silver nanoparticles (AgNPs) from ethanolic extracts of fruits (AgNPs-F) and leaves (AgNPs-L) of Annona muricata. METHODS: Previously synthesized silver nanoparticles were used for the study. The effects of the AgNPs and 5-Fluorouracil were studied on PC3, HeLa and PNT1A cells. The resazurin, migration and colonogenic assays as well as qRT-PCR were employed. RESULTS: The AgNPs-F displayed significant antiproliferative effects against HeLa cells with an IC50 of 38.58 g/ml and PC3 cells with an IC50 of 48.17 g/ml but selectively spared normal PNT1A cells (selectivity index of 7.8), in comparison with first line drug 5FU and AgNPs-L whose selectivity index were 3.56 and 2.26 respectively. The migration assay revealed potential inhibition of the metastatic activity of the cells by the AgNPs-F while the colonogenic assay indicated the permanent effect of the AgNPs-F on the cancer cells yet being reversible on the normal cells in contrast with 5FU and AgNPs-L. CASP9 was significantly over expressed in all HeLa cells treated with the AgNPs-F (1.53-fold), AgNPs-L (1.52-fold) and 5FU (4.30-fold). CXCL1 was under expressed in HeLa cells treated with AgNPs-F (0.69-fold) and AgNPs-L (0.58-fold) and over expressed in cells treated with 5FU (4.95-fold), but the difference was not statistically significant. CXCR2 was significantly over expressed in HeLa cells treated with 5FU (8.66-fold) and AgNPs-F (1.12-fold) but under expressed in cells treated with AgNPs-L (0.76-fold). CONCLUSIONS: Here we show that biosynthesized AgNPs especially AgNPs-F can be used in the development of novel and better anticancer drugs. The mechanism of action of the AgNPs involves activation of the intrinsic apoptosis pathway through upregulation of CASP9 and concerted down regulation of the CXCL1/ CXCR2 gene axis. Keywords: Silver nanoparticles, HeLa, PC3, PNT1A, CASP9, CXCL1/CXCR2