Multiscale coarse-grained molecular dynamics simulations of Wuhan, Delta, and Omicron strains of SARS-CoV-2 and novel HKU5-CoV Lineage 2

• Grant number: 25/05583-1
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 30, 2025
• End date: November 29, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Cristiane Rodrigues Guzzo Carvalho
• Grantee: Anacleto Silva de Souza
• Supervisor: Siewert-Jan Marrink
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Groningen, Netherlands
• Associated to the scholarship: 23/18211-0 - High-throughput virtual screening in the design of main protease inhibitors of the novel coronavirus, BP.PD

Abstract

A novel coronavirus with pandemic potential, designated HKU5-CoV-2, was recently identified in China. It shares notable similarities with SARS-CoV-2, the causative agent of the ongoing global COVID-19 pandemic, and has been demonstrated to pose a significant risk of human-to-human transmission. In this study, we aim to advance the understanding of the molecular and structural mechanisms in process of SARS-CoV-2 infection and its variants, including the newly characterized HKU5-CoV-2 lineage, through computational modeling and coarse-grained molecular dynamics (CG-MD) simulations. Led by Professor Siewert-Jan Marrink at the University of Groningen, this study focuses on the construction of coarse-grained (CG) models of viral envelopes for SARS-CoV-2 variants (Wuhan, Delta, Omicron) and the HKU5-CoV-2 lineage. These models will integrate structural proteins (Nucleocapsid, Membrane, Envelope), lipids, and glycosylation patterns in Spike protein, enabling the simulation of molecular dynamics over extended timescales (from microseconds to milliseconds) of the entire virus particles. The methodology involves de novo modeling of the dimeric M and the application of geometric constraints derived from Cryo-EM data. CG-MD simulations utilizing the Martini 3 force field will be employed to explore envelope morphology, protein clustering, and lipid interactions. The BEPE scholarship candidate brings experience in the field of MD simulation and statistical analysis, with publication in internationally recognized journals, and expertise in coronavirus research. The Groningen University contributions have had a global impact, evidenced by high citation rates and widespread international recognition and Professor Marrink, a leader in MD-CG simulation studies, has over 58,000 citations in Google Scholar and 341 publications indexed in the Web of Science Core Collection, with more than 41,000 citations in Web of Science, reflecting his influence in the field. Notably, the development of the Martini force field, by Marrink and collaborators, has revolutionized the CG-MD simulation of viral and cellular structures, facilitating the efficient study of complex biological processes. This BEPE proposal will provide novel information into the molecular mechanisms of viral infection, evolution, immune evasion, and antibody resistance, all of which are integral to the development of more effective therapeutic strategies and vaccines. Additionally, the findings are expected to offer a comprehensive understanding of the supramolecular organization of viral envelope proteins and the influence of mutations on vaccine-induced antibody resistance, advancing our knowledge of coronavirus as well as its novel lineages with pandemic potential.