Reviving an Ineffective Class of COVID Drugs
People who can’t mount a strong immune response to the COVID vaccines currently have limited options for protection. Available antivirals for COVID like Paxlovid interact with other drugs, making them less safe for immunocompromised people, and coronavirus variants have evolved to become resistant against previously effective monoclonal antibody treatments.
But a study published in Immunity offers hope. Lihong Liu, PhD, and David Ho, MD, of Columbia’s Aaron Diamond AIDS Research Center, and colleagues identified two new monoclonal antibodies that neutralize all current variants, making the antibodies prime candidates for development into new COVID drugs for people with weak immune systems.
In the study, the researchers took sera from patients who had COVID in February and March of 2021 and screened the samples against 12 different coronavirus variants. These experiments identified two antibodies that could neutralize all variants tested, including the XBB strains that currently account for the majority of COVID cases. When the two antibodies were administered to hamsters, they successfully prevented infection by the BA.1 variant.
The researchers then used cryoelectron microscopy to visualize how these two antibodies attach to the spike protein of the virus. They discovered that the antibodies targeted regions of the coronavirus’ spike protein that are rarely mutated among the variants currently circulating.
“Antibody treatments have been ineffective for COVID since early 2023 because the virus is evolving so quickly,” says Ho. “These antibodies have features that may be more resilient to mutational changes in the coronavirus variants. This could help accelerate the development of new longer lasting treatments for COVID, which are urgently needed for millions of immunocompromised people.”
|Cryoelectron microscopy was used to visualized how the antibodies attached to the spike protein of the virus.|
The paper, titled "Antibodies targeting a quaternary site on SARS-CoV-2 spike glycoprotein prevent viral receptor engagement by conformational locking," was published in the Oct. 10 issue of Immunity.
Lihong Liu, PhD, is assistant professor of medical sciences at Columbia University’s Vagelos College of Physicians and Surgeons.
David D. Ho, MD, is the Clyde'56 and Helen Wu Professor of Medicine, professor of microbiology & immunology, and director of the Aaron Diamond AIDS Research Center.