Clinical laboratories continue to report positive COVID-19 tests for individuals that have been vaccinated and even previously infected with the same variant of the coronavirus
Researchers across the globe continue to study the SARS-CoV-2 coronavirus and its many variants. Their goals are to curb the spread of the disease and develop new therapies and treatments for optimal patient outcomes. Now, a study conducted by scientists at the University of Missouri (UM) provides deeper insight into the processes the virus uses to mutate and overpower the human immune system. These findings could lead to improved antivirals and clinical laboratory tests for COVID-19.
The UM team identified specific mutations occurring within the virus’ spike protein that help Omicron subvariants evade existing antibodies and create an infection. These mutations may explain why some people who have had previous COVID-19 infections and/or who are fully vaccinated continue to test positive for SARS-CoV-2, and why the virus continues to evolve.
“Omicron now has more than 130 sublineages and they have been here for quite a while. We are now just finally able to detect them and differentiate among them with this research,” said Kamlendra Singh, PhD, associate research professor in the Department of Veterinary Pathobiology at UM’s College of Veterinary Medicine, in a UM press release.
“Previous variants, including Alpha, Beta, Gamma, and Delta, contributed to many of the mutations occurring now with these Omicron variants. So, our research shows how the virus has evolved over time with new mutations,” he added.
“Throughout the pandemic, the [SARS-CoV-2] virus has continued to get smarter and smarter. Even with vaccines, it continues to find new ways to mutate and evade existing antibodies,” said Kamlendra Singh, PhD (above), Associate Research Professor, College of Veterinary Medicine at University of Missouri, in a UM press release. This research team’s findings may help clinical laboratories further develop their SARS-CoV-2 antibody tests. (Photo copyright: University of Missouri.)
Antibodies for One Variant, but Not for Another
The scientists began their investigation by researching online databases that track COVID-19 cases and analyzing the protein sequences from more than 10 million Omicron-related samples that were collected from around the world since November of last year.
They examined the available sequences, structures of spike/receptor and spike/antibody complexes of the samples, and then conducted molecular dynamics simulations. The team utilized 3D modeling to locate where mutations occur and created structures of the spike protein to determine how the mutations are affected by antibodies and vaccinations.
The researchers found that the Omicron variant continues to mutate and has become extremely efficient at adaptation. Reinfections are happening because many individuals do not possess the antibodies for the new subvariants that continue to develop.
“Vaccinated individuals, or those who have previously tested positive, may have the antibodies for one variant but not necessarily for any of the other variants,” Singh explained. “The various mutations may seem like only subtle differences, but they are very important.”
The UM scientists’ research shows it is possible to differentiate Omicron subvariants from each other and pinpoint how certain mutations might become problematic for patients. According to Singh, many people can be infected with multiple variants at the same time. He is hopeful that their work will make it possible for vaccines and other treatments to specifically target different strains of the virus.
Singh also believes that the coronavirus is most likely never going to disappear from society and that new variants and their sublineages will continue to appear and evolve.
“The ultimate solution going forward will likely be the development of small molecule, antiviral drugs that target parts of the virus that do not mutate,” Singh said. “While there is no vaccine for HIV, there are very effective antiviral drugs that help those infected live a healthy life, so hopefully the same can be true with COVID-19.”
Omicron Subvariants May Be Here to Stay
“I am proud of my team’s efforts, as we have identified specific mutations for various variants throughout the pandemic, and it feels good to be contributing to research that is assisting with the situation,” Singh said. “We will continue to help out, as there will surely be new variants in the future.”
Singh is also part of a team that developed a supplement called CoroQuil-Zn, which was designed to reduce a patient’s viral load after being infected with SARS-CoV-2. The drug is currently being used in parts of India and is awaiting approval from the US Food and Drug Administration (FDA).
Clinical laboratories that perform antibody testing for SARS-CoV-2 infections should be aware that the coronavirus will likely be moving among humans for many years to come. This recent research may aid in the development of new antivirals, treatments, and vaccines that target specific subvariants for the best patient outcomes.
Many of the mutations were found at sites on the spike protein where antibodies bind, which may explain why the Omicron variant is more infectious than previous variants
Scientists at the University of Missouri (UM) now have a better understanding of why the SARS-CoV-2 Omicron variant is more infectious than previous variants and that knowledge may lead to improved antivirals and clinical laboratory tests for COVID-19.
As the Omicron variant of the coronavirus spread across the globe, scientists noted it appeared to be more contagious than previous variants and seemed resistant to the existing vaccines. As time went by it also appeared to increase risk for reinfection.
The UM researchers wanted to know why. They began by examining the Omicron variant’s mutation distribution, its evolutionary relationship to previous COVID-19 variants, and the structural impact of its mutations on antibody binding. They then analyzed protein sequences of Omicron variant samples collected from around the world.
“We know that viruses evolve over time and acquire mutations, so when we first heard of the new Omicron variant, we wanted to identify the mutations specific to this variant,” said Kamlendra Singh, PhD, Associate Research Professor, Department of Veterinary Pathobiology at UM’s College of Veterinary Medicine (CVM), in a UM press release.
Kamlendra Singh, PhD (above), an associate research professor in the Department of Veterinary Pathobiology at UM’s College of Veterinary Medicine, led the team that identified 46 mutations of the SARS-CoV-2 Omicron variant. “I went to India last April and I got infected by the Delta variant. So, it then became personal to me,” he told NBC affiliate KOMU. The UM team hopes their findings lead to improvements in existing COVID-19 antivirals and clinical laboratory tests. (Photo copyright: University of Missouri.)
In their paper, the UM team wrote, “Here we present the analyses of mutation distribution, the evolutionary relationship of Omicron with previous variants, and probable structural impact of mutations on antibody binding. … The structural analyses showed that several mutations are localized to the region of the S protein [coronavirus spike protein] that is the major target of antibodies, suggesting that the mutations in the Omicron variant may affect the binding affinities of antibodies to the S protein.”
There are a total of 46 highly prevalent mutations throughout the Omicron variant.
Twenty-three of the 46 mutations belong to the S protein (more than any previous variant).
Twenty-three of 46 is a markedly higher number of S protein mutations than reported for any SARS-CoV-2 variant.
A significant number of Omicron mutations are at the antibody binding surface of the S protein.
“Mutation is change in the genome that results in a different type of protein,” Singh told NBC affiliate KOMU. “Once you have different kinds of protein after the virus and the virus attacks the cell, our antibodies do not recognize that, because it has already been mutated.”
Omicron Mutations Interfere with Antibody Binding
Of the 46 Omicron variant mutations discovered by the UM researchers, some were found in areas of the coronavirus’ spike protein where antibodies normally bind to prevent infection or reinfection.
“The purpose of antibodies is to recognize the virus and stop the binding, which prevents infection,” Singh explained. “However, we found many of the mutations in the Omicron variant are located right where the antibodies are supposed to bind, so we are showing how the virus continues to evolve in a way that it can potentially escape or evade the existing antibodies, and therefore continue to infect so many people.”
These findings explain how the Omicron variant bypasses pre-existing antibodies in a person’s blood to cause initial infection as well as reinfection.
The UM team hopes their research will help other scientists better understand how the SARS-CoV-2 coronavirus has evolved and lead to future clinical laboratory antiviral treatments.
“The first step toward solving a problem is getting a better understanding of the specific problem in the first place,” Singh said. “It feels good to be contributing to research that is helping out with the pandemic situation, which has obviously been affecting people all over the world.”
Singh and his team have developed a supplement called CoroQuil-Zn designed to reduce a patient’s viral load after being infected with the SARS-CoV-2 coronavirus. The drug is currently being used in parts of India and is awaiting approval from the US Food and Drug Administration (FDA).
New discoveries about SARS-CoV-2 and its variants continue to further understanding of the coronavirus. Research such as that performed at the University of Missouri may lead to new clinical laboratory tests, more effective treatments, and improved vaccines that could save thousands of lives worldwide.
