ACE2 antibodies are specialized proteins that interact with the Angiotensin-Converting Enzyme 2 (ACE2) receptor, a protein found on the surface of various cells throughout the human body. Their ability to specifically target and influence the ACE2 receptor is expanding our knowledge of how the body functions and responds to external threats.
The ACE2 Receptor and Antibodies
The ACE2 receptor is a protein present on the surface of many cell types, including those in the lungs, heart, blood vessels, kidneys, liver, and gastrointestinal tract. It functions as an enzyme, breaking down larger proteins, particularly angiotensin II, into smaller molecules that help regulate blood pressure and inflammation.
Antibodies, also known as immunoglobulins, are Y-shaped proteins produced by the immune system to identify and neutralize foreign substances called antigens. Each antibody has a unique binding site that specifically recognizes and attaches to a particular antigen, similar to a lock and key. This binding action can either directly neutralize the antigen or tag it for destruction by other immune cells.
An ACE2 antibody targets the ACE2 receptor. These antibodies can be naturally occurring within the body or engineered in a laboratory. Their interaction with the ACE2 receptor allows them to influence its normal functions or block unwanted interactions.
How ACE2 Antibodies Function
ACE2 antibodies exert their effects through several mechanisms, primarily by interfering with the ACE2 receptor’s interactions. One significant way they function is by physically blocking the binding of other molecules to the ACE2 receptor. For instance, in the context of viral infections, an ACE2 antibody can prevent a virus from attaching to the receptor, thereby inhibiting its entry into host cells.
Some ACE2 antibodies achieve neutralization by binding to the receptor-binding domain (RBD) of a viral spike protein, which is the part of the virus that normally docks with ACE2. This binding prevents the virus from engaging with the ACE2 receptor on human cells, rendering it unable to initiate infection.
While some ACE2 antibodies directly inhibit ACE2 enzymatic activity, others, like hACE2.16, can block viral binding without interfering with the enzyme’s normal function.
Roles in Health and Disease
ACE2 antibodies hold significant implications for understanding and combating various diseases, particularly viral infections. The ACE2 receptor serves as a primary entry point for coronaviruses like SARS-CoV and SARS-CoV-2, which causes COVID-19. The spike protein of SARS-CoV-2 binds directly to ACE2, initiating infection in host cells.
In the context of COVID-19, ACE2 antibodies can act as therapeutic agents by blocking the SARS-CoV-2 virus from binding to the ACE2 receptor on human cells. This mechanism prevents viral entry and subsequent infection. Researchers have developed antibodies, such as 87G7 and hACE2.16, that effectively neutralize SARS-CoV-2 variants, including Omicron, by targeting the ACE2-binding site.
The development of such antibodies provides a promising strategy to prevent or treat viral infections by disrupting the initial step of cellular invasion. These antibodies can also be used as diagnostic tools to detect the presence of the virus or assess the immune response in infected individuals. The research into ACE2 antibodies is ongoing, with efforts focused on developing robust and broadly effective treatments that are resilient to viral mutations.
Beyond viral infections, ACE2 and its antibodies are also involved in regulating the renin-angiotensin system (RAS), which controls blood pressure and fluid balance. Dysregulation of ACE2 activity can contribute to conditions such as hypertension and cardiovascular disease. Therefore, ACE2 antibodies could offer therapeutic avenues for these conditions by modulating ACE2 function.