Researchers discover tiny antibody that blocks COVID-19 virus

An international team of researchers led by scientists from the University of Pittsburgh School of Medicine has developed a tiny antibody that can block the development and spread of the virus that causes COVID-19. 

The researchers isolated the antibody and used it to construct a drug that at a very low dose was able to neutralize the COVID-19 virus in experiments with mice and hamsters. The drug, called ab8, has potential as both a treatment and a preventative.

The effectiveness of ab8 is possible because its small size allows it to better penetrate the infection sites. The antibody is 10 times smaller than the full-sized antibody found in the convalescent plasma from people who recovered from the coronavirus.

The research was published Oct. 15 in the journal Cell. 

The small size also gives it an advantage for treating respiratory virus infections, the paper notes, because it can penetrate tissue, especially if it's delivered by inhalation.

The ab8 treatment in the animals not only reduced amount of virus in the lungs and relieved the pneumonia, but also reduced virus shedding in the upper airway. This means ab8 has the potential for reducing the spread of the virus.

Ab8 was effective, the researchers found, even at a small dose of 3 milligrams/kilogram of body weight. They note that the smaller size also has the advantage of requiring production of smaller amounts of the drug.

The researchers used electron microscopy to look at how ab8 interfered with the ACE2 (angiotensin-converting enzyme 2) binding site for the virus.

This is the first time, the authors say, that a high-potency human antibody has been validated as effective against the virus in two animal models. However, the authors note, higher doses might be necessary in treatment of humans.

Senior author Dimiter Dimitrov, working at the University of Pittsburgh, had previously isolated antibodies that were effective against the SARS virus in 2003, and later against other infectious diseases.

He and his colleagues used their huge "library" of antibodies to hunt for suitable antibody genes for COVID-19. They compare their search method to "panning" for gold.

The process selected the antibodies that had the highest affinity for binding to the spike (S) protein of the virus.

The researchers discovered that ab8 was specific and did not have polyreactivity. In other words, it does not bind to "5,300 human membrane proteins," which means that it is less likely to cause any side effects in the body.

Ab8 also may be able to target the COVID-19 virus in its various conformations at the same time.

Co-author Dr. John Mellors, chief of the Division of Infectious Diseases at the University of Pittsburgh Medical Center, said in a university news release: “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. 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.”

The Cell paper concludes that ab8's unique binding target and "mechanism of neutralization could also help in the discovery of more potent inhibitors and vaccines."