April 07, 2021

New research from Victor Padilla-Sanchez, a postdoctoral research scientist at The Catholic University of America, analyzes COVID-19 structures to understand why the UK, South Africa, and Brazil variants appear to be more infectious than the original novel coronavirus. Padilla-Sanchez’s research is being conducted within the Biology Department’s Bacteriophage T4 Lab.

There are currently more than 4,000 variants of COVID-19. “The UK, South Africa, and Brazil variants are more contagious and escape immunity easier than the original virus,” said Padilla-Sanchez in Research Ideas and Outcomes. “We need to understand why they are more infectious and, in many cases, more deadly.”

Padilla-Sanchez’s research paper called "SARS-CoV-2 Structural Analysis of Receptor Binding Domain New Variants from United Kingdom and South Africa," was published in Research Ideas and Outcomes in January 2021. He discusses the UK and South African variants and presents a computational analysis of the structure, which studies the virus's crystal structure and molecular dynamics by looking at the spike glycoprotein bound to the ACE2 receptor where the mutations have been introduced. The paper outlines the reason why these variants bind better to human cells.

"This was a very fast project — the computational study lasted one month," he said. "There are many other labs doing wet lab experiments, but there aren't many computational studies. That's why I decided to do this important work now."

All viruses mutate as they make copies of themselves to spread and thrive, SARS-CoV-2, the virus that causes COVID-19, is no different. The UK variant, also known as B.1.1.7, was first detected in September 2020, and is now causing 98%of all COVID-19 cases in the United Kingdom. The World Health Organization says B.1.1.7 is one of several variants of concern along with others that have emerged in South Africa and Brazil.

According to Padilla-Sanchez, the current vaccines will not necessarily treat the variants. "The variants will require their own specific vaccines. We'll need as many vaccines [as there are] variants that appear."

All three variants have undergone changes to their spike protein — the part of the virus which attaches to human cells. As a result, they are better at infecting cells and spreading.

"I've been analyzing a recently published structure of the SARS-CoV-2 spike bound to the ACE2 receptor and found why the new variants are more transmissible," he said. "These findings have been obtained using UC San Francisco Chimera software and molecular dynamics simulations using the Frontera supercomputer of the Texas Advanced Computing Center."

Padilla-Sanchez found that the UK variant has many mutations in the spike glycoprotein, but most important is one mutation, N501Y, in the receptor binding domain that interacts with the ACE2 receptor. "This N501Y mutation provides a much higher efficiency of binding, which in turn makes the virus more infectious. This variant is replacing the previous virus in the United Kingdom and is spreading in many other places in the world," he said.

The South Africa variant emerged in October 2020, and has more important changes in the spike protein, making it more dangerous than the UK variant. It involves a key mutation — called E484K — that helps the virus evade antibodies and parts of the immune system that can fight coronavirus based on experience from prior infection or a vaccine. Since the variant escapes immunity the body will not be able to fight the virus. "We're starting to see the South Africa variant here in the U.S.," he said.

Padilla-Sanchez will continue to research the changes taking place with SARS-CoV-2.