Identification of Phytochemicals with Inhibitory Potential Against Beta-lactamase Enzymes via Computer-aided Approach.

INTRODUCTION: Antibacterial drugs have been widely used for the past century to treat diseases, but their efficacy has been limited by multi-resistant pathogens, particularly those that utilize beta-lactamase enzymes. The inhibition of beta-lactamase enzymes holds great promise for reducing the influence of such pathogens. OBJECTIVE: This study aims to evaluate the mechanism of inhibition of phytochemicals with antibacterial activity against two classes of beta-lactamases using computational methods. METHODS: To achieve this objective, a total of thirty phytochemicals were docked against SHV-1 beta-lactamase and AmpC beta-lactamase after procurement from Protein Data Bank. The pharmacokinetics (ADMET) and density functional theory (DFT) analysis study were also conducted to unravel the nature of the top six most promising compounds on each protein. RESULTS: The results showed that a significant percentage of the compounds had binding affinities greater than that of avibactam, the positive control. Quercetin-3-O-rutinoside showed the most promising results against SHV-1 beta-lactamase with an affinity of -9.4 kcal/mol, while luteolin was found to be the most promising candidate against AmpC beta-lactamase with an affinity of -8.5 kcal/mol. DFT analysis demonstrated the reactivity of these compounds, and the ADMET study indicated that they were relatively safe. CONCLUSION: In conclusion, the study's findings suggest that the selected compounds have significant potential to inhibit beta-lactamase and may be used in combination with antibiotics against organisms that produce beta-lactamase. This study provides a basis for further research in a wet-lab setting to validate the results.

Strengthening Africa's capacity for vaccine research: Needs and challenges.

Vaccine development and production harbinger the control and eradication of infectious diseases. Vaccination played a huge role in the curtailment of disease outbreaks like smallpox and polio, especially in Africa. Despite the high demand for several vaccines in Africa due to the highly infectious disease burden, the continent still lacks adequate capacity for vaccine research and development. This paper aims to discuss the need and challenges of Africa to strengthen its capacity for vaccine research and development and also highlight practical recommendations. Some of the needs for Africa to prioritize vaccine research and development include; improving quality of life and well-being, cost-effectiveness, independent preparedness and response to local outbreaks, and increased access to funding. Challenges associated with vaccine research and development include the cost of the investment, risk of failure; poor ethical framework and legislation; lack of adequate funding; lack of political will & support; and poor surveillance system. Strategies to create sufficient research funds, an efficient surveillance system, and a legislative framework are clearly described. In conclusion, strengthening vaccine research capacity in Africa requires the political goodwill of African governments and strategic partnerships with international organizations and institutes. The challenges facing this development and possible solutions have been highlighted in this article.