Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen causing the coronavirus disease (COVID-19) pandemic, continues to wreak havoc around the world. To date, worldwide infections have reached more than 226 million, and more than 4.65 million people have lost their lives.
For scientists to deal with the outbreak, they need to know more about the structure of SARS-CoV-2 and how it infects the body.
Now researchers from the Garvan Institute of Medical Research, Darlinghurst Australia, CSIRO Data61 and the School of Biotechnology and Biomolecular Sciences (UNSW) have presented the most comprehensive analysis of the three-dimensional structure of SARS-CoV-2, providing new insight into how the virus infects cells and replicates.
This Aquaria page summarizes and maps all available 3D structural information for all proteins that make up the COVID-19 virus (SARS-CoV-2).
3D structures of all SARS-CoV-2 proteins
In the study published in the Biology of molecular systems journal, the team modeled the 3D structures of all SARS-CoV-2 proteins, yielding more than 2,000 models that cover 69% of the viral proteome. These models provide details not found anywhere else.
The different structures involved the 27 proteins of the coronavirus. Additionally, the analysis identified viral proteins that copy and hijack human proteins, allowing the virus to evade cellular defenses and replicate to trigger infection.
The SARS-CoV-2 envelope modeled in Aquaria. Image credit: Garvan Institute of Medical Research
Study results showed that approximately 6% of the proteome mimics human proteins, while approximately 7% is involved in processing human proteins, thereby reversing post-translational modifications, disabling the defenses of the host and blocking host translation.
The team made the structural models freely available on the Aquaria-COVID Resource, a website designed to help researchers discover potential new targets on the virus to develop treatments or vaccines. Models can also help scientists study new emerging variants.
Focus on SARS-CoV-2
Amid the pandemic, many scientists focused on SARS-CoV-2, including its structures like viral proteins. Specifically, they focused on the spike glycoprotein, the one responsible for binding to the human angiotensin-converting enzyme 2 (hACE2) receptor.
SARS-CoV-2 RNA synthesis complex modeled in Aquaria. Image credit: Garvan Institute of Medical Research
Some modeling studies have predicted 3D structures for the entire SARS-CoV-2 proteome, using technologies like AlphaFold, I-TASSER, Rosetta, SWISS-MODEL and MODELLER. However, some of these models provided variable predictions, raising concerns about accuracy.
Scientists sought to address these limitations through the use of a depth-based strategy that models all states with associated 3D structures. 3D protein structures provide atomic resolution data on the composition of SARS-CoV-2. This is essential for developing treatments and vaccines that target specific structures of the virus.
The results of the study showed that three coronavirus proteins, NSP3, NSP16 and NSP13, mimicked human proteins. These proteins, called mimics, allow the virus to evade the immune system, affecting COVID-19 outcomes.
In addition, the team also identified five other proteins, namely NSP1, NSP3, spike glycoprotein, ORF9b protein and envelope protein, collectively known as hijackers, which invade and disrupt cellular processes. As a result, the virus takes over to complete its life cycle and invade other cells.
The team also determined eight coronavirus proteins that can self-assemble called teams, providing new insights into how the virus replicates its genome.
“We found structural evidence of viral protein interaction for 29% of the viral proteome, including eight SARS-CoV-2 proteins,” the team explained.
That leaves 14 of the 27 viral proteins in a category called suspects. These proteins are thought to play a key role in infection but have no structural evidence of interaction with other proteins.
In a nutshell, the study gathered information about the structure of the viral proteome that was not available from other resources.
“Our analysis of these data provided insight into how viral proteins self-assemble, how NSP3 and NSP13 can mimic human proteins, and how viral hijacking reverses post-translational modifications, blocks translation of the ‘host and disables host defenses,’ the researchers concluded in the study.
The study may help scientists develop effective treatment options and vaccines to fight the pandemic.