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.
The researchers published their findings in the International Journal of Molecular Sciences, titled, “Complex Mutation Pattern of Omicron BA.2: Evading Antibodies without Losing Receptor Interactions.”
“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.
—JP Schlingman
Related Information:
Complex Mutation Pattern of Omicron BA.2: Evading Antibodies without Losing Receptor Interactions
Spike Protein Changes Explain Repeat COVID Infections
Mizzou Research Examines Why COVID-19 Omicron Variant Is So Transmissible: ‘It Can Escape’
Scientists Estimate 73% of US Population May Be Immune to SARS-CoV-2 Omicron Variant