Project RE-ENVELOP, Mechanistic Modeling of TSWV Envelope Dynamics: Identifying Novel Lipid-Binding Vulnerabilities in Specific Proteins to Combat Resistance-Breaking Strains in North Carolina

Abstract

Rajendra Nath Dasari and Shail Sakalabhaktula

Tomato Spotted Wilt Virus (TSWV) is a major agricultural pathogen in North Carolina affecting tobacco, tomato, and pepper production, with emerging resistance-breaking (RB) strains compromising traditional genetic defenses. Unlike most plant viruses, TSWV is enveloped and depends on a host-derived lipid bilayer for stability, infectivity, and transmission via thrips vectors. This study introduces Project RE-ENVELOP, a computational framework integrating AlphaFold-Multimer modeling and molecular dynamics-inspired simulations to characterize lipid–protein interactions governing viral envelope stability. We focus on glycoprotein (Gn/Gc) transmembrane anchoring, nucleocapsid (N) protein lipid-binding pockets, and envelope lipid composition. We further introduce a Python-based stability proxy system to quantify rigidity zones and thermal denaturation behavior under North Carolina field conditions. Results identify mutation-sensitive lipid anchoring regions, cationic lipid-binding hotspots, and temperature-dependent envelope destabilization thresholds. Finally, we propose a low-cost colorimetric gel matrix device (“Envelop-Scan”) as a field- deployable proxy sensor for envelope integrity. This work reframes TSWV vulnerability as a biophysical lipid-interface problem rather than a purely genomic one, opening novel avenues for antiviral crop protection strategies.

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