Simulations could help design nanocontainers used in drug delivery

Each simple RNA virus has a genome, its “native RNA”. This genome dictates how the virus replicates in cells to eventually cause disease. The genome also has the code to make a capsid, the protein shell of a virus that encapsulates the genome and protects it like a nanocontainer.

A team led by Roya Zandi, professor of physics and astronomy at the University of California, Riverside, has developed a theory and performed a series of simulations that may help explain how a virus finds its native genome and how capsids form around it and not around other RNAs in the cell.

“A better understanding of how capsids form is of vital importance to materials scientists and a crucial step in the design of engineered nano-shells that could serve as vehicles to deliver drugs to specific targets in the body,” Zandi said.

The work of the researchers, published in ACS Nanoshows that the interplay of protein mechanical properties, genome size, and the strength of the interaction between genome and capsid proteins can significantly alter capsid symmetry, structure, and stability.

When a virus enters a cell, the capsid opens to release the genome, which then uses the cell’s reproductive machinery to replicate. Newly formed genomes begin to acquire their capsids, a process primarily driven by the attractive electrostatic interaction between positive charges on capsid proteins and negative charges on genomes. But how the virus selects and packages its native RNA in the crowded environment of a host cell cytoplasm in the presence of numerous nonviral RNAs and other polymers has remained a mystery.

Simulations conducted by Zandi’s team show that capsid proteins could, in theory, choose any non-viral genome to encapsulate. But the viral genome, she said, is best suited for capsid proteins to form a shell around due to an interaction of energies at the molecular level.

“The stress distribution of capsid proteins is lower when capsids encapsulate their own genome, the one they were coded for,” Zandi said. “The energy of the whole system is lower. While smaller non-viral RNAs are abundantly available in the cell, capsid proteins tend to form a shell around a viral RNA because the shell resultant soccer ball shape has a lower stress distribution.”

Zandi said the work presents a systematic comparison of theory and experiments, which will provide a better understanding of the role of RNA in the assembly pathway, stability and structure of the capsid.

“A deeper understanding of the role of the genome in virus assembly mechanisms could lead to design principles for alternative antivirals,” she said.

The new work is a first step in understanding viral assembly. The process is not well understood because viruses measure in nanometers and assembly occurs in milliseconds.

“Theoretical work and simulations are needed to understand how a virus grows,” Zandi said.

Zandi was joined in the research by graduate student Sanaz Panahandeh at UCR; Siyu Li at the Songshan Lake Materials Laboratory in China; and Bogdan Dragnea at Indiana University, Bloomington. Li is a former UCR graduate student.

The research was funded by the National Science Foundation.

Source of the story:

Material provided by University of California – Riverside. Original written by Iqbal Pittalwala. Note: Content may be edited for style and length.

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