The formation of the coronavirus is successfully simulated

A UC Riverside physicist and her former graduate student have successfully modeled the formation of SARS-CoV-2, the virus that spreads COVID-19, for the first time.

In the article published in Virusesmagazine, Roy Zandi, a professor of physics and astronomy at UCR, and Xiu Li, a postdoctoral fellow at the Songshan Lake Materials Laboratory in China, offer a general understanding of the assembly and formation of SARS-CoV-2 from its constituent components.

“Understanding viral assembly has always been a key step leading to therapeutic strategies,” Zandi said. “Many experiments and simulations of viruses such as HIV and hepatitis B have had a remarkable impact on elucidating their assembly and providing tools to combat them. Even the simplest questions regarding the formation of SARS-CoV-2 remain unanswered.”

Zandi explained that the most important step in the life cycle of any virus is the packaging of its genome into new virions, or viral particles. This is a particularly challenging task for coronaviruses such as SARS-CoV-2, with their very large RNA genomes. Indeed, coronaviruses have the largest genome among viruses that use RNA as their genetic material.

SARS-CoV-2 has four structural proteins: envelope (E), membrane (M), nucleocapsid (N) and spike (S). The structural proteins M, E, and N are essential for the assembly and formation of the viral envelope, the outermost layer of the virus that protects the virus and helps facilitate entry into host cells. This process occurs on the membrane of the intermediate Golgi compartment of the endoplasmic reticulum, or ERGIC, a complex membrane system that provides the coronavirus with its lipid envelope. The assembly of coronaviruses is unique compared to many other viruses in that this process occurs on the ERGIC membrane.

Most computational studies to date use coarse-grained models, where only details important on a large scale are used to simulate viral components. Over the years, rough models have explained several viral assembly processes, leading to important discoveries.

“In this paper, using crude models, we were able to successfully simulate the formation of SARS-CoV-2: N proteins condense RNA to form a compact RNP complex that interacts with M proteins embedded in the lipid membrane,” Zandi said.

She added that “butonization,” which occurs when part of the membrane begins to bend upward, completes the formation of the virus. The model Zandi and Lee developed allowed them to investigate the mechanisms protein oligomerization, condensation of RNA with structural proteins and cell membrane-protein interactions. It also allowed them to predict the factors that control virus assembly.

“Our work reveals key ingredients and components that contribute to the packaging of the long genome of SARS-CoV-2,” Li said. “Experimental research on the specific role of each of the several structural proteins involved in the formation of viral particles is growing rapidly, but many details remain unclear.”

According to Zandi, the insight presented in the Research work and comparing the results with those observed experimentally may provide some of these details and inform the development of effective antiviral drugs to stop coronaviruses at the assembly stage.

“The physical aspects of coronavirus assembly explored in our model are of interest not only to physical scientists beginning to apply physics-based methods to the study of enveloped viruses, but also to virologists trying to identify the location of key protein interactions within the assembly and virus starters,” she said. “We now have a better understanding of which interactions are important for genome packaging and shaping virus. This is the first time we have been able to fine-tune the interaction between the genome and proteins and obtain genome condensing and assembling at the same time.’

The title of the article is “Biophysical modeling of SARS-CoV-2 assembly: genome condensation and budding”.