As the number of coronavirus infections now exceeds 120,000 people worldwide, including more than 4,000 dead, researchers are rushing to understand why the virus spreads more easily than these predecessors. Initially, authorities announced a spread factor of around 3, but it appears to be higher. Although it is still too early to decide on the average real rate, researchers at the University of Washington believe they have some answers explaining why this new coronavirus is more contagious.
Following genetic and structural analyzes, the scientists identified a key characteristic of the virus: a surface protein which could explain, at least in part, why it so easily infects human cells compared to these predecessors.
” Understanding the transmission of the virus is key to enabling containment and future prevention Said David Veesler, structural virologist at the University of Washington in Seattle, who published his team’s results on the viral protein. The study is available on the biomedical preprint server bioRxiv.
Currently, other research groups are studying the gateway through which the new coronavirus enters human tissue: a receptor located on cell membranes. Both the cell receptor and the viral protein offer potential targets for future treatments, which could block the pathogen. But according to the current state of research, it is still too early to be sure.
The new coronavirus, SARS-CoV-2, appears to be much more easily spread than the one that caused severe acute respiratory syndrome (SARS) in 2003, SARS-CoV. Indeed, SARS-CoV-2 has infected more than ten times more people. It would also be due to the fact that the new coronavirus spreads even when the carrier does not show symptoms, which was not the case in 2003.
Furin activation site: a unique feature of SARS-CoV-2
To infect a cell, coronaviruses use a “spike” (or “advanced”) protein, which binds to the cell membrane through a process activated by specific cellular enzymes. Genomic analyzes of the new coronavirus have revealed that its spike protein differs from that of close relatives, and suggest that the protein has a specific site that is activated by an enzyme in the host cell, called furin.
This is an important discovery because furin is found in many human tissues, including the lungs, liver and small intestine, which means the virus has the potential to attack multiple organs, says Li Hua, structural biologist at Huazhong University of Science and Technology in Wuhan (China), where the epidemic began.
The present discovery could also explain some of the symptoms seen in people with COVID-19, such as liver failure, says Li, co-author of a genetic analysis of the virus published on the preprint server. ChinaXiv February 23. SARS-CoV (2003) and other coronaviruses like the new one do not have furin activation sites, she said.
The furin activation site “defines the virus very differently from SARS-CoV in terms of cell penetration, and may affect the stability of the virus and therefore transmission”, explains Gary Whittaker, virologist at the University Cornell in Ithaca, New York. His team notably published another structural analysis of the coronavirus spike protein on bioRxiv, February 18.
Several other groups have also identified the site of activation as possibly allowing the virus to spread effectively between humans. They note that these sites are also found in other viruses with high human-to-human spread, including severe strains of the flu virus. On these viruses, the activation site is on a protein called hemagglutinin, not on the spike protein.
Caution
But some researchers are hesitant and don’t want to overestimate the role of the activation site in the ability of the new coronavirus to spread more easily. ” We don’t know if this will be a major problem or not Said Jason McLellan, a structural biologist at the University of Texas at Austin, also co-author of another structural analysis of the coronavirus.
Other scientists are wary of comparing the furin activation sites of influenza viruses to those of the new coronavirus. Indeed, the hemagglutinin protein on the surface of flu viruses is not similar or related to the spike protein of coronaviruses, says Peter White, virologist at the University of New South Wales in Sydney, Australia.
On the same subject: COVID-19: it can be transmitted even when the carrier has no symptoms
And the flu virus that caused the most deadly pandemic in 1918 – known commonly as the “Spanish flu” – doesn’t even have a furin activation site, says virologist Lijun Rong. University of Illinois at Chicago.
Whittaker says in particular that studies on cellular or animal models are necessary to test the function of the site of activation. ” Coronaviruses are unpredictable, and even very good assumptions can be wrong “He said. His team is currently testing how removing or changing the furin activation site affects the function of the spike protein.
Results reproduced by other teams
Li’s team is also studying molecules capable of blocking furin, which could be considered as potential therapies. But because of the epidemic, their progress is rather slow. Li lives on campus (in Wuhan) and is currently the only member of his team who can access the laboratory.
In Texas, the McLellan group identified another characteristic that could explain why the new coronavirus infects human cells so successfully. Their experiments showed that the spike protein binds to a receptor in human cells – known as the angiotensin 2 converting enzyme (ACE2) – at least ten times more tightly than the spike virus virus. SARS.
Veesler’s team also came to the same conclusion, suggesting that the receptor is another potential target for vaccines or therapies. For example, a drug that blocks the receptor could make it more difficult for coronavirus to enter cells, which could at least significantly slow the epidemic until the virus disappears.
Source: bioRxiv
–
