Computational Design of Miniprotein Binders Targeting the Viral Entry in Chikungunya and Dengue, Neglected Tropical Diseases

Neglected Tropical Diseases (NTDs) continue to be a global health concern, affecting millions worldwide. Arboviruses such as Chikungunya virus (CHIKV) and Dengue virus (DENV) are particularly threatening due to the lack of specific antiviral treatments, the continual emergence of new variants, and their mosquito vectors. These challenges underscore the urgent need for novel antiviral strategies. Here, we apply computational methods to design miniprotein binders targeting critical viral entry components: the CHIKV envelope, and DENV fusion loop. Our protocol integrates classical and deep learning-based approaches and can be generalizable to other protein targets. Promising binder candidates were further evaluated through all-atom Molecular Dynamics simulations to assess structural stability and binding interactions. We provide complete transparency and a detailed rationale for each design step to facilitate adaptation of these protocols to other neglected disease targets. While the miniproteins presented here represent promising antiviral leads, experimental validation remains essential to confirm their biological activity.