Scientists Isolate Smallest Biological Molecule to Date That Completely and Specifically Neutralizes SARS-CoV-2

The tiny antibody component is the variable, heavy chain (VH) domain of an immunoglobulin, which is a type of antibody found in the blood. It was found by “fishing” in a pool of more than 100 billion potential candidates using the SARS-CoV-2 spike protein as bait. Ab8 is created when the VH domain is fused to part of the immunoglobulin tail region, adding the immune functions of a full-size antibody without the bulk.

According to the researchers, Ab8 is highly effective in preventing and treating SARS-CoV-2 infection in mice and hamsters. Its tiny size not only increases its potential for diffusion in tissues to better neutralize the virus, but also makes it possible to administer the drug by alternative routes, including inhalation. Importantly, it does not bind to human cells - a good sign that it will not have negative side-effects in people. The researchers believe that its small size could allow Ab8 to be administered as an inhaled drug or intradermally, rather than intravenously through an IV drip, like most monoclonal antibodies currently in development.

Researchers who tested Ab8 using live SARS-CoV-2 virus found that at very low concentrations, Ab8 completely blocked the virus from entering cells. The tem further tested Ab8 at varying concentrations in mice using a modified version of SARS-CoV-2 and found that even at the lowest dose, Ab8 decreased by 10-fold the amount of infectious virus in those mice compared to their untreated counterparts. Ab8 was also effective in treating and preventing SARS-CoV-2 infection in hamsters.

“Ab8 not only has potential as therapy for COVID-19, but it also could be used to keep people from getting SARS-CoV-2 infections,” said co-author John Mellors, M.D., chief of the Division of Infectious Diseases at UPMC and Pitt. “Antibodies of larger size have worked against other infectious diseases and have been well tolerated, giving us hope that it could be an effective treatment for patients with COVID-19 and for protection of those who have never had the infection and are not immune.”

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University of Pittsburgh School of Medicine