BWC0977, a broad-spectrum antibacterial clinical candidate to treat multidrug resistant infections.

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Hameed P, Shahul, Kotakonda, Harish, Sharma, Sreevalli ORCID: 0000-0001-6055-7853, Nandishaiah, Radha, Katagihallimath, Nainesh, Rao, Ranga, Sadler, Claire, Slater, Ian, Morton, Michael, Chandrasekaran, Abhijeeth ORCID: 0000-0001-8673-2410 et al (show 39 more authors) , Griffen, Ed ORCID: 0000-0003-0859-554X, Pillai, Dhanashree, Reddy, Sambasiva, Bharatham, Nagakumar, Venkatesan, Suryanarayanan, Jonnalagadda, Venugopal ORCID: 0000-0001-6684-7739, Jayaraman, Ramesh, Nanjundappa, Mahesh, Sharma, Maitrayee, Raveendran, Savitha, Rajagopal, Sreenath ORCID: 0000-0002-5041-8814, Tumma, Harikrishna, Watters, Amy, Becker, Holly, Lindley, Jill, Flamm, Robert, Huband, Michael, Sahm, Dan, Hackel, Meredith, Mathur, Tarun, Kolamunnage-Dona, Ruwanthi ORCID: 0000-0003-3886-6208, Unsworth, Jennifer, Mcentee, Laura, Farrington, Nikki ORCID: 0000-0003-2300-9430, Manickam, Dhanasekaran, Chandrashekara, Narayana, Jayachandiran, Sivakandan, Reddy, Hrushikesava, Shanker, Sathya, Richard, Vijay, Thomas, Teby ORCID: 0000-0002-3505-977X, Nagaraj, Savitha ORCID: 0000-0003-4996-4874, Datta, Santanu ORCID: 0000-0001-5335-5276, Sambandamurthy, Vasan, Ramachandran, Vasanthi ORCID: 0000-0003-2496-179X, Clay, Robert ORCID: 0000-0002-7085-4752, Tomayko, John, Das, Shampa ORCID: 0000-0002-2540-4816 and V, Balasubramanian ORCID: 0000-0003-0473-6894 (2024) BWC0977, a broad-spectrum antibacterial clinical candidate to treat multidrug resistant infections. Nature communications, 15 (1). 8202-. ISSN 2041-1723, 2041-1723

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Abstract

The global crisis of antimicrobial resistance (AMR) necessitates the development of broad-spectrum antibacterial drugs effective against multi-drug resistant (MDR) pathogens. BWC0977, a Novel Bacterial Topoisomerase Inhibitor (NBTI) selectively inhibits bacterial DNA replication via inhibition of DNA gyrase and topoisomerase IV. BWC0977 exhibited a minimum inhibitory concentration (MIC₉₀) of 0.03-2 µg/mL against a global panel of MDR Gram-negative bacteria including Enterobacterales and non-fermenters, Gram-positive bacteria, anaerobes and biothreat pathogens. BWC0977 retains activity against isolates resistant to fluoroquinolones (FQs), carbapenems and colistin and demonstrates efficacy against multiple pathogens in two rodent species with significantly higher drug levels in the epithelial lining fluid of infected lungs. In healthy volunteers, single-ascending doses of BWC0977 administered intravenously ( https://clinicaltrials.gov/study/NCT05088421 ) was found to be safe, well tolerated (primary endpoint) and achieved dose-proportional exposures (secondary endpoint) consistent with modelled data from preclinical studies. Here, we show that BWC0977 has the potential to treat a range of critical-care infections including MDR bacterial pneumonias.

Item Type:	Article
Uncontrolled Keywords:	Animals, Humans, Mice, Rats, Gram-Negative Bacteria, Gram-Positive Bacteria, Anti-Bacterial Agents, Microbial Sensitivity Tests, Drug Resistance, Multiple, Bacterial, Adult, Middle Aged, Female, Male, Young Adult, Healthy Volunteers
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Population Health Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	07 Nov 2024 16:10
Last Modified:	30 Jun 2025 08:21
DOI:	10.1038/s41467-024-52557-2
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3187149