• How a virus packages its genetic materia

    From ScienceDaily@1:317/3 to All on Wed Mar 9 21:30:48 2022
    How a virus packages its genetic material
    Simulations could help design nanocontainers used in drug delivery

    Date:
    March 9, 2022
    Source:
    University of California - Riverside
    Summary:
    Physics and astronomy professors have 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.



    FULL STORY ==========================================================================
    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 for making a capsid, the protein shell of a virus that encapsulates the genome and protects it like a nanocontainer.


    ==========================================================================
    A team led by Roya Zandi, a 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 material scientists and a crucial step in the design of engineered nano-shells that could serve as vehicles for delivering drugs to specific targets in the body," Zandi said.

    The researchers' work, published in ACS Nano, shows that the interplay of
    the mechanical properties of proteins, the size of the genome, and the
    strength of the interaction between the genome and capsid proteins can significantly modify the symmetry, structure, and stability of the capsid.

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

    The simulations run by Zandi's team show that capsid proteins could, in
    theory, pick any nonviral genome to encapsulate. But the viral genome,
    she said, is best suited for capsid proteins to form a shell around due
    to an interplay of energies at the molecular level.



    ==========================================================================
    "The stress distribution of the capsid proteins is lower when the
    capsids encapsulate their own genome, the one for which they were coded,"
    Zandi said.

    "The energy of the whole system is lower. While smaller nonviral RNAs
    are available in the cell in plenty, the capsid proteins are inclined
    toward forming a shell around a viral RNA because the resulting soccer ball-like shell has a lower stress distribution." Zandi said the work
    lays out a systematic comparison of theory and experiments, which will
    allow a better understanding of the role of RNA in the capsid assembly
    pathway, stability, and structure.

    "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 an early step in understanding viral assembly. The
    process is not well understood because viruses measure in nanometers
    and the assembly occurs in milliseconds.

    "Theoretical work and simulations are necessary to understand how a
    virus grows," Zandi said.

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

    The research was funded by the National Science Foundation.


    ========================================================================== Story Source: Materials provided by
    University_of_California_-_Riverside. Original written by Iqbal
    Pittalwala. Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Sanaz Panahandeh, Siyu Li, Bogdan Dragnea, Roya Zandi. Virus
    Assembly
    Pathways Inside a Host Cell. ACS Nano, 2022; 16 (1): 317 DOI:
    10.1021/ acsnano.1c06335 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220309165541.htm

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