Successfully simulates the formation of coronavirus - genome cohesion and budding

For the first time, a physicist at the University of California, Riverside, and her former graduate student, Siyu Li, successfully simulated the formation
of the SARS-CoV-2 virus that spreads COVID-19.

In a paper published in the journal Viruses, the assembly and formation of SARS-CoV-2 is comprehensively understood
in terms of composition.

Zandi said: "Understanding viral assembly has been a key step
towards a therapeutic strategy.
Extensive experimentation and simulations of viruses such as HIV and hepatitis B virus have had a significant impact
on elucidating their combinations and providing the means to combat them.
Even the simplest questions about the formation of SARS-CoV-2 have no answers
.
”

Zandi explains that a key step in the life cycle of any virus is to package its genome into new virions or virions
.
This is a particularly challenging task for coronaviruses, such as SARS-CoV-2, because their RNA genomes are very large
.
In fact, of viruses that use RNA as genetic material, coronaviruses have the largest known genome
.

SARS-CoV-2 has four structural proteins: envelope protein (E), membrane protein (M), nucleocapsid protein (N), and spike protein (S).

Structural proteins M, E, and N are critical
for the assembly and formation of viral envelopes.
The outermost layer of the virus is to protect the virus and help enter the host cell
.
This process occurs on the membrane of the Golgi Middle Compartment of the Endoplasmic Reticulum (ERGIC), a complex membrane system that provides a lipid envelope for coronaviruses
.
The assembly of coronaviruses is unique compared to many other viruses because this process takes place on the
ERGIC membrane.

To date, most computational studies have used coarse-grained models, in which only the details associated with large length scales are used to simulate viral components
.
Over the years, coarse-grained models have explained several viral assembly processes, leading to important discoveries
.

"In this paper, using the coarse-grained model, we have been able to successfully mimic the formation of SARS-CoV-2: N proteins compress RNA, forming compact RNP complexes that interact
with M proteins embedded in lipid membranes," Zandi said.

She added that when part of the cell membrane begins to bend, "budding" completes the formation
of the virus.
The models developed by Zandi and Siyu Li et al.
allowed them to explore the mechanisms
of protein oligomerization, RNA condensation of structural proteins, and cell membrane-protein interactions.
This also allows them to predict the factors that control the assembly of
the virus.

"Our work reveals key components and components that help package the long genome of SARS-CoV-2," Li said
.
"Experimental research on the specific roles of several structural proteins involved in the formation of virions is proliferating, but many details remain unclear
.
"

Zandi said the insights presented in the research paper and comparing the findings with those observed by the experiment can provide some of these details and inform the design of effective antiviral drugs to suppress the coronavirus during the assembly phase
.

"The physical aspects of coronavirus assembly explored in our model are of interest not only to physical scientists who are beginning to apply physics-based approaches to envelope virus research, but also to virologists trying to locate key protein interactions in viral assembly and budding
," she said.
We now have a better understanding
of which interactions are important for genome packaging and virus formation.
This is the first time we've been able to fine-tune the interactions between genomes and proteins while obtaining genome cohesion and assembly
.
”

Biophysical Modeling of SARS-CoV-2 Assembly: Genome Condensation and Budding