SPILLOproject
Identifying Proteins to Develop Drugs with Least Toxicity

2022 saw 409,000 drug trials registered globally as of March. Like every coin has two sides, this good news is accompanied by the reported rise of adverse drug reactions (ADR), which is identified as one of the leading causes of hospitalization. Despite the time and financial resources spent on drug discovery and development, including animal testing and healthy volunteer study, pharmaceutical companies are yet to identify the biomolecular origin of ADR.

To combat this challenge, they usually turn to molecular docking software, which models the interaction between drug molecules and target proteins to characterize the behaviors of small molecules in the binding site of target proteins. However, it does not adequately include protein flexibility in the model and does not elucidate crucial information like off-target proteins in humans and other organisms, a requirement to predict ADR occurrences.

SPILLOproject, an innovative in-silico solutions provider for drug R&D and clinical pharmacology, fills this chasm of unmet clinical need. It offers SPILLO-Potential Binding Sites Searcher (SPILLO-PBSS) that performs a fast and unbiased search for drug binding sites on protein structures while considering protein flexibility. It is able to identify previously undiscovered binding sites, even when hidden or completely closed and therefore not identifiable by traditional approaches. Thereby, it showcases the biomolecular mechanisms that cause ADR both in drugs under development and the ones already on the market. This feature enables rapid analysis of the entire structural proteome of humans, mice, rats, and other organisms to identify targets and off-targets of any small molecule, saving time and resources during complex drug development processes.

“SPILLO-PBSS can improve the probability of identifying and mapping targets and off-targets of any molecule on a proteomic scale. When pharmaceutical companies approach us regarding their problems, we perform the calculations in our software tool and give them accurate results,” says Alessandro Di Domizio, Founder of SPILLOproject.

The tool displays a distinct mapping of target and off-target proteins and corresponding binding sites. It enables clients to design drug molecules that do not interact with adverse reaction causing off-targets, while preserving the molecule-target binding affinities that lead to therapeutic effects. This information can be crucial in designing and developing drugs with the least toxic impact on individuals, irrespective of their varied protein expression levels. SPILLO-PBSS is also instrumental in drug discovery and development by identifying therapeutic targets of interest in-silico and finding new uses of molecules (drug rescue and drug repurposing), allowing pharmaceutical industries to secure profitable ROI.

Clients can turn to SPILLOproject to analyze the whole structural proteome of humans and other animals to highlight the molecules’ potential target and off-target proteins. With access to protein 3D structures of various organisms from the RCSB Protein Data Bank and AI-predicted AlphaFold Protein Structure Database, the software accurately studies model organism that shares the same protein as humans to perform in-vivo experiments. This feature allows pharmaceutical companies to avoid unreliable animal testing, saving time and resources during drug trials.

SPILLO project strives to help pharmaceutical companies improve human health using its innovative computational technologies. For instance, the in-silico solutions provider was sought to identify the biomolecular origin of a molecule with an anti-glioblastoma effect, as the client could not do so with traditional methods or tools. Using SPILLO-PBSS, it identified two target proteins responsible for the anti-glioblastoma effect along with the binding sites. The results were also experimentally validated by the University of Milano-Bicocca, Italy. The client received a grant to develop new molecules with improved binding affinities for the targets identified by SPILLOproject.

Established in 2016, SPILLOproject aims to improve human health and advance research on diseases, including rare and neglected ones, by developing and leveraging innovative technologies like SPILLO-PBSS. It has made significant progress in optimizing drug discovery and development processes. Not just from word-of mouth, the software’s ability to detect binding sites even in highly distorted proteins is validated by academic centers and published in peer-reviewed scientific journals. This instrumental factor drives pharmaceutical companies to trust SPILLOproject and its team of interdisciplinary experts for real-life issues of drugs in the market or currently in the developmental stage.