NEW YORK (Reuters Health) – Scientists believe they have discovered why SARS-CoV-2, the virus that causes COVID-19, is so much more infectious than SARS-CoV-1, which caused the 2003 SARS outbreak.
“Through a series of large scale computer simulations comparing SARS-CoV-1 and 2, we observed that the two are actually are very different dynamically. And this is not just the part of the protein that binds to the human receptor, this is the entire protein,” Dr. Mahmoud Moradi, of the University of Arkansas, Fayetteville, noted in a phone interview with Reuters Health.
“This has some implications in terms of vaccine and therapeutic development because we know that we shouldn’t just focus on certain parts of the protein. There are other parts of protein that are very important and you would not actually know that if you just focus on the static picture,” Dr. Moradi said.
He presented his research February 25 at the Biophysical Society virtual annual meeting.
The first step in coronavirus infection is for the virus to enter cells. For this to happen, the spike proteins on the outside of the coronavirus must reposition. While the position of the “inactive” and “active” states of the spike proteins of both the SARS-CoV-1 and SARS-CoV-2 are known, Dr. Moradi’s team wanted to study how the spikes moved from one position to another and the dynamics of those movements.
This research would not have been possible without “very large supercomputer allocations” from the COVID-19 High Performance Computing (HPC) Consortium, a unique public-private effort to make supercomputing power available to researchers working on projects related to COVID-19, Dr. Moradi said.
“We discovered in these simulations that SARS-CoV-1 and SARS-CoV-2 have completely different ways of changing their shape, and on different time scales. SARS-CoV-1 moves faster, it activates and deactivates, which doesn’t give it as much time to stick to the human cell because it’s not as stable. SARS-CoV-2, on the other hand, is stable and ready to attack,” Dr. Moradi explains in a conference statement.
“The active state of the SARS-CoV-2 is actually much more stable than the active state of SARS-CoV-1, which gives it a better chance of binding to the human receptor,” he told Reuters Health.
“Also the dynamics is much slower for SARS-CoV-2 in general. So SARS-CoV-1 goes back and forth between the active and inactive state very often, but SARS-CoV-2 is very slow in that sense, which again, gives it a better chance of binding because it’s more stable,” he said.
The team also identified a specific region at the end of the spike protein, called the N-terminal domain (NTD), that is the key difference between SARS-CoV-1 and -2. “This is the part of the protein that not many people have paid attention to before, but it turns out that this is a very important part for the stability of the protein,” Dr. Moradi said. Mutations in that region could affect the transmissibility, he noted.
It may be possible to “design therapeutics that alter the dynamics and make the inactive state more stable, thereby promoting the deactivation of SARS-CoV-2. That is a strategy that hasn’t yet been adopted,” Moradi said in the news release.
His team has now begun studying the new SARS-CoV-2 B.1.1.7 variant in the lab to detect differences in its movements.
SOURCE: http://bit.ly/3bHID1X Biophysical Society Annual Meeting 2021, presented February 25, 2021.
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