Evaluation of MMV Pandemic Response Box compounds to identify potent compounds against clinically relevant bacterial and fungal clinical isolates .

BACKGROUND

Multidrug resistant bacterial and fungal pathogens are resistant to a number of significant front-line drugs, hence, identification of new inhibitory agents to combat them is crucial. In this study, we aim to evaluate the activity of Pandemic Box compounds from Malaria Medicines Venture (MMV) against and bacterial, fungal clinical isolates.

METHODS

Isolates were initially screened with 201 antibacterial and 46 antifungal compounds (10 μM) using a microbroth dilution in triplicates to determine MIC. A persister assay was performed for bacterial pathogens.

RESULTS

Out of 201 antibacterial compounds, twenty-nine and seven compounds inhibited the growth of and at 10 μM, respectively. MMV1580854, MMV1579788, eravacycline and epetraborole inhibited both the bacterial test isolates. In a persister assay, MMV1634390 showed complete bactericidal effect against . With antifungal activity compounds, responded to15 compounds, Six compounds inhibited and one was effective against at 10 μM. The ratio of Minimum Fungicidal Concentration (MFC): Minimum Inhibitory Concentration (MIC) of MMV1782110 was 2 against . . Eberconazole, amorolfine and luliconazole are fungicidal targeting at a MFC: MIC ratio of 2.

CONCLUSION

Five compounds from MMV Pandemic Box were found to be inhibiting colistin and ceftazidime resistant clinical isolate, also against colistin and β-lactam resistant clinical isolate MMV1634390 showed complete bactericidal effect against in a persister assay. MMV1782110, Eberconazole, amorolfine and luliconazole exhibited potent anti-fungal activity. Further investigations are warranted to identify the targets and mechanism.