Chikungunya virus (CHIKV) replication relies on the multifunctional nsP2 protein, making it an attractive target for antiviral drug discovery. Here, we report the resolution of oxaspiropiperidine 1, a first-in-class inhibitor of the CHIKV nsP2 RNA helicase (nsP2hel), into its constitutive enantiomers and characterization of their antiviral activity. The enantiomer (R)-1 exhibited potent inhibition of viral replication, nsP2hel ATPase activity, and dsRNA unwinding, while the (S)-1 enantiomer was >100-fold less active. The (R)-1 enantiomer also demonstrated a high selectivity for CHIKV over other RNA viruses and for nsP2hel over other RNA helicases. Direct binding of (R)-1 to the nsP2hel protein was confirmed by 19F NMR. Biophysical and structural studies revealed conformational polymorphism in the spirocyclic scaffold of (R)-1, suggesting a potential role of thermal mobility of the ligand in allosteric inhibition of nsP2hel. Collectively, these findings designate (R)-1 (RA-NSP2-1) as a high-quality chemical probe and (S)-1 (RA-NSP2-1N) as a negative control for probing the biology of alphavirus RNA helicases.
The comparison of adopter and non-adopter sample reveals three potential adoption inhibitor, security, data privacy, and portability, which underlines the importance of the technical and security perspectives for research investigating the adoption of technology.
Nattakarn Phaphoom, Xiaofeng Wang, S. Samuel et al.· Journal of Systems and Softw...· 111 citations· ⚡8
This study investigates how Lean internal startup facilitates software product innovation in large companies and identifies its enablers and inhibitors, and shows the potential of the method-in-action framework to investigate the Lean startup approach in non-startup context.
Henry Edison, Nina M. Smørsgård, Xiaofeng Wang et al.· Journal of Systems and Softw...· 78 citations· ⚡6
This paper highlights the challenges to conduct proper affect-related studies with psychology, provides a comprehensive literature review in affect theory, and proposes guidelines for conducting psychoempirical software engineering.
D. Graziotin, Xiaofeng Wang, P. Abrahamsson· SSE@SIGSOFT FSE· 56 citations· ⚡4
This study conducts a multiple case study on twenty European software startups and proposes a prototype-centric learning model in early stage software startups, and identifies factors that occur as barriers but also facilitators for prototyping in earlystage software startups.
Anh Nguyen-Duc, Xiaofeng Wang, P. Abrahamsson· International Conference on...· 44 citations· ⚡5
It is demonstrated that linker-free PROTACs can outperform traditional designs, marking a paradigm shift in PROTAC development for targeted protein degradation.
Pinal, a 16-billion-parameter foundation model that produces protein candidates from natural-language functional descriptions, supports natural language as a high-level interface for candidate generation in protein design, enabling programmable exploration with reduced reliance on manually specified structural or seque...
A new machine-learning framework aims to improve the success rate of computational protein design while moving away from results that reproduce sequences found in nature.
