Pitt scientists developing drug to prevent, treat COVID-19

Henrietta Brewer
September 16, 2020

Scientists at the University of Pittsburgh School of Medicine (UPMC) have isolated an antibody, dubbed Ab8, that is 10x smaller than a full-sized antibody used in drugs and completely neutralizes the SARS-CoV-2 virus.

The researchers, along with scientists at the University of North Carolina at Chapel Hill, University of Saskatchewan, the University of Texas Medical Branch at Galveston and the University of British Columbia, will be evaluating Ab8 and its efficacy. The drug is seen as a potential preventative against SARS-CoV-2. This is good because it means that it will not have negative side-effects in humans.

Researchers say that by having a small size, this molecule increases the ability of the tissue to neutralize the coronavirus.

One of the world's largest efforts to find effective COVID-19 treatments will evaluate the impact of REGN-COV2, an investigational antibody cocktail, on mortality, hospital stays, and the need for ventilation. In a membrane protein array assay, the team found that ab8 did not bind to any of the 5,300 human membrane-associated proteins, suggesting that it is highly specific and therefore has a low potential for off-target toxicities in vivo.

Alternatively, antibody domains and fragments such as fragment antigen binding (Fab), single-chain variable fragment (scFv), and heavy-chain variable domain (VH) are attractive formats for candidate therapeutics due to their low molecular mass (under 50 kDa).

It was combined with part of the immunoglobulin tail area to create Ab8, without the bulk of a full-size antibody.

Like the Pitt and UPMC vaccine candidate PittCoVacc that delivers an immunization through a spiky Band-Aid-like patch and overcomes the need for needles and refrigeration, the researchers are "thinking outside the box" when it comes to how Ab8 could be administered.

"Its small size might allow it to be given as an inhaled drug or intradermally, rather than intravenously through an IV drip, like most monoclonal antibodies now in development", the report says.

Dimitrov's team has since discovered antibodies that battle a host of other infectious diseases including MERS, dengue, Hendra and Nipah viruses.

The drug's foundation is a tiny but potent antibody that can block the virus from infecting cells.

"Ab8 not only has potential as a therapy for COVID-19, but it also could be used to keep people from getting SARS-CoV-2 infections", said M.D. John Mellors, study's co-author and chief of the Division of Infectious Disease at UPMC and Pitt. In mice trials, those treated with Ab8 had 10-fold less of the amount of infectious virus compared to those that were untreated.

Development of the antibody began in February at Pitt's Center for Antibody Therapeutics, Mellors said, "before covid-19 was a household name".

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