Scientists have discovered a protein that neutralizes coronavirus without side effects

Scientists from the University of Pittsburgh have discovered a tiny antibody component that has been shown to be highly effective in preventing and treating SARS-CoV-2 infection in animals. Pittwire.

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Scientists from the University of Pittsburgh School of Medicine have isolated the smallest biological molecule to date that completely neutralizes the SARS-CoV-2 virus, which is the cause of COVID-19. This antibody component, which is 10 times smaller than the full-length antibody, has been used to create a drug known as Ab8 for potential use as a therapeutic and prophylactic agent against SARS-CoV-2.

As researchers report in a publication in the journal Cell, Ab8 is highly effective in preventing and treating SARS-CoV-2 infection in mice and hamsters. Its tiny size not only increases the ability to diffuse into tissues, which helps better neutralize the virus, but also allows the drug to be administered through alternative routes, including inhalation. Importantly, it does not bind to human cells—a good sign that the drug will not have negative side effects in humans.

Ab8 was evaluated jointly with scientists from the University of North Carolina at Chapel Hill (UNC) and the University of Texas Medical Branch (UTMB) at Galveston, as well as the University of British Columbia and the University of Saskatchewan.

“Ab8 not only has the potential to treat COVID-19, but could also be used to prevent people from becoming infected with SARS-CoV-2,” said co-author John Mellors, head of infectious diseases at the University. “The larger antibodies work against other infectious diseases and are well tolerated, giving us hope that this could be an effective treatment for patients with COVID-19 and protection for those who have never had the infection and are not immune.”

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The tiny antibody component is the heavy chain variable domain (VH) of immunoglobulin, which is a type of antibody found in the blood. It was discovered by fishing through 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 tail region of an immunoglobulin, adding the immune functions of a full-length antibody without the bulk.

The small size may allow Ab8 to be administered as an inhaled formulation or intradermally rather than intravenously via an IV drip like most monoclonal antibodies currently in development.

Abound Bio, a newly formed company backed by UPMC, has licensed Ab8 for worldwide development.

Dimiter Dimitrov, senior author of the Cell publication and director of the University's Antibody Therapy Center, was one of the first to discover neutralizing antibodies to the original SARS coronavirus in 2003. In the years that followed, his team discovered potent antibodies against many other infectious diseases, including those caused by the MERS-CoV, dengue, Hendra and Nipah viruses. Antibodies against Hendra and Nipah viruses have been tested in humans and approved for clinical use in Australia.

Clinical trials are testing convalescent plasma, which contains antibodies from people who have already had COVID-19, and can serve as a treatment for those fighting the infection. But plasma is not enough for everyone who might need it, and its effectiveness has not been proven.

That is why Dimitrov and his team decided to isolate the gene for one or more antibodies that block the SARS-CoV-2 virus, which would allow the drug to be mass produced. In February, Wei Li, associate director of the Center for Therapeutic Antibodies and co-director of the study, began analyzing large libraries of antibody components made from human blood samples and found several therapeutic antibody candidates, including Ab8, in record time.

A team from the UTMB Center for Biosecurity and Emerging Diseases and Galveston National Laboratory then tested Ab8 using the live SARS-CoV-2 virus. At very low concentrations, Ab8 completely blocked the penetration of the virus into cells. With these results in hand, the UNC team tested Ab8 at various concentrations in mice using a modified version of SARS-CoV-2. Even at the lowest dose, Ab8 reduced the amount of virus in these mice 10-fold compared to their untreated counterparts. Ab8 has also been effective in treating and preventing SARS-CoV-2 infection in hamsters, according to scientists from the University of Saskatchewan. Researchers at the University of British Columbia have discovered a unique way that Ab8 is so effective at neutralizing the virus using sophisticated electron microscopy techniques.

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“The COVID-19 pandemic is a global challenge facing humanity, but biomedical science and human ingenuity are likely to help overcome it,” said Mellors, professor emeritus of medicine who holds an award for excellence in HIV and AIDS therapy. “We hope that the antibodies we discovered will contribute to this triumph.”

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