Digital discovery of antimicrobial molecules from marine Arctic resources with reduced risk of triggering resistance
Background
DigiBiotics is a research and innovation initiative built on two awarded grants.
- AntiBioSpec – a trans-faculty strategic project awarded by UiT the Arctic University of Norway
- DigiBiotics – a Digital Life Norway call awarded by the Research Council of Norway.
Summary
Antimicrobial resistance is currently causing around 700 000 deaths annually, with an estimated rise to 10 million over the next 30 years. Continuous development of antimicrobial compounds with new modes of action is essential to reduce the threat posed by antimicrobial resistance. DigiBiotics will meet this challenge by exploring new compounds inspired by marine Arctic natural products and developing novel experimental and computational methods for determining molecular structure and dynamics, and interplay with bacteria. This will allow for a better understanding of drug-target interactions and provide an atomic resolution for drug development against novel targets. Promising compounds will be refined to a level suitable for continued sustainable drug development in the pharmaceutical industry.
The goal of DigiBiotics is to translate innovative scientific discoveries into commercially attractive propositions by combining in-depth scientific knowledge with a broad understanding of the requirements of successful drug discovery and development. This goal will be reached by fulfilling five scientific objectives and one training objective:
• Digitally mine genomes, isolate and identify novel antimicrobial molecules from Arctic marine microorganisms with a selection of compounds less prone to trigger resistance development
• Create, develop and validate experimental and computational methods for determination of molecular structure, absolute configuration and conformation.
• Provide, through new computational and experimental methods, an in-depth understanding of structure-activity relationships for “middle-space molecules” enabling optimization of their biological activity
• Compute quantitative structure activity relationships (QSAR) for knowledge-driven refinement of antimicrobial molecules into compounds with acceptable pharmacokinetics, optimizing potency, absorption, distribution and metabolic properties.
• Define the microbial targets and resistance development to provide feedback for refined design.
• Train young scientists in the cross-disciplinary skills needed for future successful drug discovery
Transdisciplinary approach
An important element of DigiBiotics will be to connect and collaborate with different stakeholders, including, in addition to the research community, 
industry, healthcare service organizations and professionals, and public administrators (Figure 3). Political and societal awareness on the threat of antimicrobial resistance is crucial to stimulate the implementation of measures to get the misuse of antibiotics and to stimulate innovation.