New consortium aims to comprehend principles underlying the formation of coronaviruses

Overview

• Post By : Kumar Jeetendra


• Source: University of California - Riverside


• Date: 10 Dec,2020

“This consortium will aim to comprehend the physical principles underlying the formation of coronaviruses,” said Roya Zandi, a professor of physics and astronomy at UC Riverside and the principal investigator of this four-year project that received funding of over $1.75 million. “We will also explore the effect of some drugs on the assembly process.”

Zandi is an expert on the physics and biophysics principles of virus formation. Her lab researches the statistical mechanics of virus assembly, the dynamics of the self-assembly process, and how various mechanisms can influence the stability of the viral structure.

While in vitro experiments and computer simulations of viruses have improved scientists’ understanding of the viruses’ formation and how to combat them, there have been no similar studies aimed at understanding coronavirus assembly.

The three campuses will work together to understand the factors contributing to the formation of SARS-COV-2.

In UCR, scientists will use atomic force microscopy, or AFM, a powerful technique that can image almost any type of surface, together with super-resolution and confocal microscopy to study the assembly of SARS-COV-2 within cell-like vesicles.

Zandi clarified that UCR’s single-molecule investigations will be paired with UC Merced studies that explore the bulk properties of cell membranes interacting with viral proteins.

UCR scientists, she added, will perform in vitro studies and in vivo microscopy studies of virus-like particle assembly inside living cell lines and tissue culture. Virus-like particles are supramolecular protein assemblies that may have applications in synthetic biology and medicine.

To interpret the experimental data and provide predictions of possible therapeutic targets for suppressing viral self-assembly, the consortium will use all-atom molecular dynamics simulations developed at UC Davis and coarse-grained simulations and analytical concepts developed at UCR and UC Merced to study the multimerization — the practice of assembling aggregates of multiple molecules — of structural proteins, the interaction of membranes with proteins, and protein-protein interactions resulting in the formation of virus.

Mohideen will study the assembly pathway and interaction mechanisms between the viral proteins and RNA using AFM single-molecule investigations. Kaul and Kuhlman will design in vivo experiments and will also study the effects of changing the intracellular pH on the assembly of virus-like particles.

Zandi said the consortium’s quantitative studies and its focus on the close integration of theory and experiment will distinguish its function from other comparable biological and biochemical studies.

“Our strength and uniqueness are in the use of multidisciplinary and synergistic basic science approaches to identify critical steps and components of viral assembly, which will open avenues to look for drugs that can potentially disrupt the crucial assembly steps,” she said. “While we’ll spend the next four years understanding the creation of coronaviruses and, in particular, SARS-CoV-2, our final goal is to develop a multicampus institute, based on the principles of physical virology, that will establish UC’s leadership in this emerging field.”