TACC’s Frontera supercomputer assists in building infection models of COVID-19 variants.
All viruses mutate as they make copies of themselves to spread and thrive. SARS-CoV-2, the virus that causes COVID-19, is not proving to be any different. There are currently more than 4,000 variants of COVID-19, which has killed more than 2.7 million people worldwide during the pandemic.
The UK variant, also known as B.1.1.7, was first detected in September 2020 and is now causing 98 percent of all cases of COVID-19 in the UK. And it appears to be gaining firm control in some 100 other countries that it has spread to in recent months, including France, Denmark and the United States.
The World Health Organization states that B.1.1.7 is one of several variants of concern, along with others that have emerged in South Africa and Brazil.
“The UK, South Africa and Brazil variants are more contagious and escape immunity more easily than the original virus,” said Victor Padilla-Sanchez, a research scientist at the Catholic University of America. “We need to understand why they are more infectious and, in many cases, more deadly.”
All three variants have undergone changes in their peak protein – the part of the virus that binds to human cells. As a result, they are better at infecting cells and spreading.
In a research article published in January 2021 in Search ideas and results, Padilla-Sanchez discusses the UK and South Africa variants in detail. It presents a computational analysis of the structure of the peak glycoprotein linked to the ACE2 receptor where the mutations were introduced. His article describes the reason why these variants bind better to human cells.
“I’ve been analyzing a recently published structure from the peak of SARS-CoV-2 attached to the ACE2 receptor and found out why the new variants are more transmissible,” he said. “These findings were obtained using UC San Francisco Chimera software and molecular dynamics simulations using the Texas Advanced Computing Center (TACC) Frontera supercomputer.”
Padilla-Sanchez found that the UK variant has many mutations in the peak glycoprotein, but the most important is a mutation, N501Y, in the receptor-binding domain that interacts with the ACE2 receptor.
Victor Padilla-Sanchez, research scientist at the Catholic University of America. Credit: The Catholic University of America
“This N501Y mutation provides much greater binding efficiency, which in turn makes the virus more infectious. This variant is replacing the previous virus in the UK and is spreading to many other places in the world, ”he said.
The South Africa variant emerged in October 2020 and has more important changes in the peak protein, making it more dangerous than the UK variant. It involves a key mutation – called E484K – that helps the virus avoid antibodies and parts of the immune system that can fight the coronavirus based on previous infection or a vaccine experience. Once the variant escapes immunity, the body will not be able to fight the virus. “We are starting to see the South African variant here in the United States,” he said.
Padilla-Sanchez carried out a structural analysis, which studied the virus’s crystalline structure; and molecular dynamics to obtain these results.
“The main computational challenge in doing this research was to find a computer powerful enough to do the task of molecular dynamics, which generates very large files and requires a large amount of memory. This research would not have been possible without the Frontera supercomputer, ”said Padilla-Sanchez.
According to Padilla-Sanchez, current vaccines will not necessarily treat variants. “The variants will require their own specific vaccines. We will need as many vaccines for the variants that appear. “
In the future, Padilla-Sanchez will continue to research the changes that are occurring with SARS-CoV-2.
“This was a very quick project – the computer study lasted a month,” he said. “There are many other laboratories doing wet laboratory experiments, but there are not many computational studies. That’s why I decided to do this important job now. “
This study, called “SARS-CoV-2 Structural Analysis of Receptor Binding Domain New Variants from United Kingdom and South Africa”, was published in Search ideas and results in January 2021. The researcher who worked on this study is Victor Padilla-Sanchez, from the Catholic University of America.
Reference: “SARS-CoV-2 Structural Analysis of Receptor Binding Domain New Variants of the United Kingdom and South Africa” by Victor Padilla-Sanchez, January 15, 2021, Search ideas and results.
DOI: 10.3897 / rio.7.e62936