Programme

P.78 -- Posters, VCTP-51

Date: Thursday, 6 August 2026

Time: 09:30 - 10:30

A Hierarchical Binding Mechanism Governs the SARS-CoV-2 N Protein-G3BP1 Interaction: A Computational Insight

Hoang Linh Nguyen1,2,*, Nguyen Quoc Thai3,*, O My Na4,5 and Mai Suan Li6,*

1Institute of Fundamental and Applied Sciences, 6 Tran Nhat Duat, Tan Dinh Ward, Duy Tan University, Ho Chi Minh City 700000, Vietnam 2 School of Engineering and Technology, Duy Tan University, Da Nang 550000, Vietnam 3Dong Thap University, 783 Pham Huu Lau Street, Cao Lanh Ward, Dong Thap 870000, Vietnam 4Faculty of Applied Science, Ho Chi Minh City University of Technology (HCMUT), 268 Ly Thuong Kiet, Dien Hong Ward, Ho Chi Minh City 700000, Vietnam 5Vietnam National University, Ho Chi Minh City 700000, Vietnam 6Institute of Physics, Polish Academy of Sciences, al. Lotnikow 32/46, 02-668, Warsaw, Poland *Email: nguyenhoanglinh9@duytan.edu.vn, nqthai@dthu.edu.vn, masli@ifpan.edu.pl

The sequestration of host G3BP1/2 by the SARS-CoV-2 nucleocapsid (N) protein is vital for viral antagonism of the cellular stress response. While N-terminal residues 14–17 are critical for this interaction, the atomistic determinants defining viral variant affinities remain ambiguous. Integrating umbrella sampling and molecular dynamics simulations, we elucidate a hierarchical binding mechanism wherein a primary electrostatic anchor (Asp22) is locked by a secondary hydrophobic interface (Phe17). Our calculations reveal that the F17A mutation exerts a significantly more detrimental effect on binding than the Omicron P13L mutation or the direct removal of the electrostatic anchor (D22A). Crucially, F17A induces an allosteric collapse: the loss of the hydrophobic contact triggers backbone rearrangements that displace the critical Asp22 anchor. In contrast, D22A selectively abrogates the electrostatic interaction while preserving the hydrophobic core, resulting in a less severe affinity loss. These findings identify Phe17 as a structural linchpin allosterically controlling the primary electrostatic interaction, providing a detailed rationale for the mutational landscape of this viral-host interface

Presenter: Nguyễn Hoàng Linh