As a virologist specializing in SARS-CoV-2 replication and stress granule biology, I am eager to participate in the 2nd Hong Kong Laureate Forum to engage with leading scientists and fellow young researchers. My work focuses on the interaction between the G3BP1 RNA-binding protein and the SARS-CoV-2 nucleocapsid protein, uncovering novel mechanisms that regulate viral replication. By engineering a virus mutant that disrupts this interaction, I have demonstrated its critical role in pathogenesis and identified potential antiviral strategies.

This Forum presents a unique opportunity to exchange ideas on RNA biology, virus-host interactions, and translational virology, bridging fundamental research with therapeutic development. I look forward to discussing my findings with experts, gaining insights into innovative methodologies, and exploring interdisciplinary approaches that may enhance antiviral research. Additionally, learning about Hong Kong’s latest scientific advancements and connecting with a global network of researchers will foster collaborations that can drive impactful discoveries.

By participating, I aim to contribute my expertise while broadening my perspective on cutting-edge virology and molecular biology. I am excited to engage in thought-provoking discussions, refine my scientific vision, and be inspired by pioneers shaping the future of biomedical research.

Ras-GTPase-activating protein SH3-domain-binding proteins (G3BP) are multifunctional RNA-binding proteins that can exhibit both proviral and antiviral activities across different viral infections. The SARS-CoV-2 nucleocapsid (N) protein has been reported to bind strongly to G3BP, inhibiting stress granule (SG) formation and neutralizing G3BP's antiviral functions. In this study, we engineered a SARS-CoV-2 mutant, RATA, which lacks the G3BP1-N interaction, leading to a significant attenuation of viral replication in multiple cell lines and a reduction in pathogenesis in a mouse model of severe COVID-19, highlighting the importance of G3BP1-N interaction in SARS-CoV-2 infection. Additionally, we discovered that G3BP-N complexes are targeted to the pore complex of double membrane vesicles (DMVs), where nascent viral RNA is released. These complexes also facilitate localized translation of viral mRNAs at replication sites through interactions with 40S ribosomal subunits. Our study offers a detailed mechanistic understanding of the proviral roles of G3BP1 in SARS-CoV-2 replication, emphasizing its potential as a target for therapeutic intervention.