According to the World Health Organization, drug resistance is one of the biggest threats to global health in 2019, with multi-drug resistant superbugs including methicillin-resistant Staphylococcus aureus (MRSA) becoming one of the most serious concerns. A research team led by Dr Ma Cong from the Department of Applied Biology and Chemical Technology partnered with experts from the Chinese University of Hong Kong’s Faculty of Medicine to develop a new class of antibiotic candidates "Nusbiarylins". They demonstrate much effective abilities of inhibiting bacterial growth than commonly used antibiotics, yet with no toxicity to human cells. The innovation has won the Global Innovation Award at the TechConnect World Innovation Conference and Expo 2019.

Innovative antimicrobial mechanism

Existing antibiotics mostly fight against bacteria by disrupting its DNA synthesis or protein functions. Instead, the research team focused on designing new small molecules to inhibit the interaction between two proteins, NusB and NusE, which is greatly related to the growth of bacterial cells. Based on the structural information of NusB and NusE, the team developed a new pharmacophore model to screen about 5,000 small molecule compounds with drug-like compounds. Among the shortlisted compounds, (E)-2-{[(3-ethynylphenyl)imino]methyl}-4-nitrophenol (MC4) demonstrated stronger antibacterial abilities than the commonly used antibiotics with no significant toxicity against human cells.

A new class of antibiotic candidates

The research team then conducted structural modifications to optimise MC4 and synthesised 167 analogues. This new class of compounds is named "Nusbiarylins" based on their target protein "NusB" and "biaryl" structure. Laboratory test has shown its better antibacterial activity than even vancomycin – the "last resort" antibiotic drug. Pre-clinical trial studies of Nusbiarylins on human cells also showed nearly no hemolysis and excellent intestine absorption, indicating that it is safe for injection and effective for oral taking. The team believes that "Nusbiarylins" will further develop into a new class of antibiotics to fight superbugs.

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