Deciding is not always easy. And sometimes it is especially hard. But since “hard” is not really our thing (something our easy-to-use software reflects as well), we decided this time to simply rationalize the difficulty away: instead of crowning just one project, we are celebrating two winners of the BioSolveIT Scientific Challenge.
With two outstanding contributions from antiviral research, we want to show how different successful paths in computer-aided drug discovery can look, and how powerfully innovative ideas, structure-based design, and the right tools can work together. Both projects demonstrated in impressive ways how scientific challenges can be transformed into promising results through creativity and smart workflows.
Below, we are pleased to introduce both winning projects.
Winner Project by Christoph Grathwol
Fragment-based Design of ZIKV Protease Inhibitors using Publicly Available Molecules
This project demonstrated how a smart combination of fragment-based design, virtual screening, and chemical space exploration can open new paths toward antiviral discovery. Focusing on the Zika virus protease, Christoph built a efficient workflow that moved from publicly available molecules and structural insights to experimentally confirmed binders. The project is a strong example of how BioSolveIT tools can support rapid idea generation, prioritization, and validation in early-stage drug discovery.
Key summary
- Focus: Developing inhibitors for Zika virus protease using fragment-based design and virtual screening.
- Key approach: Combined crystallographic fragment screening, fragment growing (SeeSAR), virtual screening (HYDE), and Chemical Space Docking.
- Achievements: 11 structurally confirmed Zika protease binders.
- Fragment screening: 14 crystallographic hits identified; expanded via SeeSAR design.
- Virtual screening: ~16,800 Molecule Archive compounds screened; 18 advanced to crystal soaking.
- Chemical Space Docking® (C-S-D): Yielded additional hits, with Enamine-sourced compounds validated structurally.
- In vitro results: One intermediate showed weak inhibition (20% @ 50 µM), signaling early promise.
- Overall: Strong breadth in hit identification and structural confirmation.
- Software: Heavy use of SeeSAR, HYDE, infiniSee, and others for integrated design.
Christoph’s project also relied heavily on the Molecule Archive as a core part of its compound-source infrastructure. The Molecule Archive is a KIT-based academic platform that collects, stores, and redistributes research compounds so they can be reused in future scientific studies.
Winner Project by Jasmin Cara Aschenbrenner
Hit-to-Lead Development of Inhibitors of the Chikungunya Virus nsP3 Macrodomain
Jasmin’s approach highlighted the power of iterative hit-to-lead design guided by structural biology and practical synthesis strategies. Targeting the Chikungunya virus nsP3 macrodomain, she translated rich fragment-screening data into a focused medicinal chemistry campaign, generating and refining follow-up compounds with experimental confirmation along the way. The project stands out as a compelling example of how computational workflows can help transform fragment hits into increasingly promising lead matter.
Key summary
- Focus: Hit-to-lead development for the Chikungunya virus nsP3 macrodomain.
- Key approach: Started from 109 fragment hits (crystallographic screen) around the ADPr-binding site.
- Achievements: Synthesized ~99 follow-up compounds; 9 confirmed binders from the sulfolane series.
- Methods: Used BioSolveIT tools to design >2500 scaffolds via fragment merging, linking, and growing.
- Challenges: Only 64 building blocks were available, limiting synthesis to ~250 compounds.
- Crystal soaking: Achieved 9 ligand-bound structures, primarily sulfolane derivatives.
- Follow-up: Linked sulfolane scaffolds with additional adenine-site hits; obtained two new structures and a 4°C thermal shift.
- Current stage: Antiviral testing ongoing, GCI assay still being refined.
- Overall: Clear hit-to-lead progression, structural validation, and iterative design cycles.
- Software: SeeSAR, HYDE, FlexX, PoseView, and more used throughout the design process.
Jasmin’s project has progressed to the point where follow-up compounds were designed, synthesized, and structurally validated, with additional antiviral testing currently underway.All available structures have been made publicly accessible through Diamond’s interactive Fragalysis platform, where the results can already be explored in detail.
In this spirit, we wish both winners nothing but the very best for the future and sincerely appreciate their outstanding contribution to the BioSolveIT Scientific Challenge!