Abzymes Unveiled: Understanding COVID-19’s Impact

Under the direction of Steven L. Zeichner, MD, Ph.D. of UVA, researchers discovered that COVID-19 may cause the bodies of certain individuals to produce antibodies that behave similarly to the body’s natural enzymes, which are used to control vital processes like blood pressure. Associated enzymes also control vital bodily processes like inflammation and blood coagulation.

To block these “abzymes” from having negative consequences, doctors might be able to target them. Doctors should target the abzymes to address the challenging and occasionally puzzling symptoms of COVID-19 and long COVID at the source rather than just treating the downstream symptoms if abzymes with rogue activities are also accountable for some of the characteristics of long COVID.

“Some patients with COVID-19 have serious symptoms, and we have trouble understanding their cause. We also have a poor understanding of the causes of long COVID,” Zeichner, a UVA Children’s pediatric infectious disease specialist, stated.

“Antibodies that act like enzymes are called ‘abzymes.’ Abzymes are not exact copies of enzymes and so they work differently, sometimes in ways that the original enzyme does not. If COVID-19 patients are making abzymes, it is possible that these rogue abzymes could harm many different aspects of physiology. If this turns out to be true, then developing treatments to deplete or block the rogue abzymes could be the most effective way to treat the complications of COVID-19.”

Comprehending COVID-19 enzymes

The protein known as the Spike protein is present on the surface of the COVID-causing virus, SARS-CoV-2. Angiotensin Converting Enzyme 2, or ACE2, is a protein that the virus binds to on the surface of cells when infection progresses. Angiotensin II is a protein that ACE2 cuts to produce angiotensin 1-7, a derivative protein that aids in blood pressure regulation.

Whereas angiotensin 1-7 relaxes blood arteries and lowers blood pressure, angiotensin II constricts blood vessels and raises blood pressure.

Zeichner and colleagues hypothesized that certain patients could produce antibodies against the Spike protein, which bears a striking resemblance to ACE2, and indeed, this is precisely what they observed in the antibodies’ enzymatic activity.

More recently, other teams have discovered that certain individuals with prolonged COVID have issues with both their coagulation and another mechanism known as “complement.” The body’s enzymes that cut other proteins to activate them regulate both the complement system and the coagulation system.

It may be possible to determine the cause of some long-lasting COVID symptoms and the reason why they continue long after the body has recovered from the initial infection if people with protracted COVID produce enzymes that activate proteins that regulate functions like inflammation and coagulation. It might help clarify the infrequent COVID-19 vaccine adverse effects.

To ascertain if antibodies may be having unanticipated consequences in COVID-19 patients, Zeichner and his colleagues analyzed plasma samples taken from 67 volunteers with moderate to severe COVID-19 on or around day 7 of their hospitalization. The findings were contrasted with plasma that was obtained in 2018 before the pandemic started. The findings demonstrated that a tiny portion of COVID patients possessed antibodies with an enzyme-like function.

Zeichner points out that although our knowledge of the possible involvement of enzymes in COVID-19 is still developing, enzymatic antibodies have previously been found in some HIV infections. Therefore, there is precedence for a virus to cause the creation of an enzyme. It also implies that other viruses might have comparable consequences.

Zeichner anticipates that UVA’s recent discoveries may rekindle interest in the study of abzymes in medicine, as he is working on a universal coronavirus vaccine. Additionally, he expects that better treatments for people with both acute and chronic COVID-19 will result from his research.

“We now need to study pure versions of antibodies with enzymatic activity to see how abzymes may work in more detail, and we need to study patients who have had COVID-19 who did and did not develop long COVID,” he said.

“There is much more work to do, but I think we have made a good start in developing a new understanding of this challenging disease that has caused so much distress and death around the world. The first step to developing effective new therapies for a disease is developing a good understanding of the disease’s underlying causes, and we have taken that first step.”

The journal mBio has published the research team’s findings.

For more information: ACE-2-like enzymatic activity is associated with immunoglobulin in COVID-19 patients, mBio, https://journals.asm.org/doi/10.1128/mbio.00541-24