A physicist at the University of California, Riverside, and her graduate student have successfully modeled the formation of SARS-CoV-2, the virus that spreads COVID-19, for the first time.
In a paper published in Viruses, a journal, Roya Zandi, a professor of physics and astronomy at UCR, and Siyu Li, a postdoctoral researcher at Songshan Lake Materials Laboratory in China, offer an overall 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. “Numerous experiments and simulations of viruses such as HIV and hepatitis B virus have had a remarkable impact on elucidating their assembly and providing means to combat them. Even the simplest questions regarding the formation of SARS-CoV-2 remain unanswered.”
Zandi explained that a critical step in the life cycle of any virus is the packaging of its genome into new virions or virus particles. This is an especially challenging task for coronaviruses, like SARS-CoV-2, with their very large RNA genomes. Indeed, coronaviruses have the largest genome known for a virus that uses RNA as its 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 at the membrane of the Endoplasmic Reticulum Golgi Intermediate Compartment, or ERGIC, a complex membrane system that provides the coronavirus its lipid envelope. The assembly of coronaviruses is unique compared to many other viruses as this process occurs at the ERGIC membrane.
Most computational studies to date use coarse-grained models were only details relevant at large length scales are used to mimic viral components. Over the years, the coarse-grained models have explained several virus assembly processes leading to important discoveries.
“In this paper, using coarse-grained models, we have been able to successfully model the formation of SARS-CoV-2: the N proteins condense the RNA to form the compact ribonucleoprotein complex, an assembly of molecules containing both protein and RNA,” Zandi said. “This complex interacts with the M proteins that are embedded in the lipid membrane.”
She added that “budding,” which is when a part of the membrane starts to curve up, completes the virus formation. The model Zandi and Li developed allowed them to explore mechanisms of protein oligomerization, RNA condensation by structural proteins, and cellular membrane-protein interactions. It also allowed them to predict the factors that control virus assembly.
“Our work reveals key ingredients and components contributing to the packaging of the long genome of SARS-CoV-2,” Li said. “The experimental studies regarding the specific role of each of the several structural proteins involved in the formation of viral particles are soaring but many details remain unclear.”
According to Zandi, the insight presented in the research paper and the comparison of the findings with those observed experimentally could provide some of these details and inform the design of effective antiviral drugs to arrest coronaviruses in the assembly stage.
“The physical aspects of coronavirus assembly explored within our model are of interest not just to physical scientists beginning to apply physics-based methods to the study of enveloped viruses, but also to virologists attempting to locate the key protein interactions in virus assembly and budding,” she said. “We now have a better understanding of what interactions are important for the packaging of the genome and the formation of the virus. This is the first time we have been able to fine-tune the interaction between the genome and proteins and obtain the genome condensation and the assembly simultaneously.”
The research was funded by the National Science Foundation and the University of California Multicampus Research Programs and Initiatives.
The title of the paper is “Biophysical Modeling of SARS-CoV-2 Assembly: Genome Condensation and Budding.”

How to resolve AdBlock issue?
UK scientists have made a fundamental breakthrough in the quest to predict fluctuations in the rotation of the Earth accurately and so the length of the day - potentially opening up new predictions for the effects of climate change.
Rubisco (Ribulose-1,5-bisphosphate carboxylase/oxygenase) is responsible for providing carbon for almost all life on Earth. Rubisco functions by converting atmospheric CO2 from the Earth’s atmosphere to organic carbon matter, which is essential to sustain most life on Earth.
University of Nottingham scientists have used machine learning to find new ways to identify and pinpoint diseases in poultry farms, which will help to reduce the need for antibiotic treatment, lowering the risk of antibiotic resistance transferring to human populations.
New supercomputer simulations show that truly Earth-like exoplanets with oceans and continents, and beaches along the boundaries, may be much more common around red dwarfs than previously expected. This means ongoing and future exoplanet survey missions can expect to find multiple Earth-analogs for further study before the end of the decade.