Wei Li, Ph.D., of Pitt, demonstrates a step in the process of obtaining a potential drug against COVID-19.

University of Pittsburgh School of Medicine scientists have isolated the smallest biological molecule to date that completely and specifically neutralizes the SARS-CoV-2 virus, which is the cause of COVID-19.

The researchers report today (September 14, 2020) in the journal Cell that Ab8 is highly effective in preventing and treating SARS-CoV-2 infection in mice and hamsters.

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

“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.

It was found by “fishing” in a pool of more than 100 billion potential candidates using the SARS-CoV-2 spike protein as bait.

Dimiter Dimitrov, Ph.D.

Dimiter Dimitrov, Ph.D., senior author of the Cell publication and director of Pitt’s Center for Antibody Therapeutics, was one of the first to discover neutralizing antibodies for the original SARS coronavirus in 2003.

That’s why Dimitrov and his team set out to isolate the gene for one or more antibodies that block the SARS-CoV-2 virus, which would allow for mass production.

Then a team at UTMB’s Center for Biodefense and Emerging Diseases and Galveston National Laboratory, led by Chien-Te Kent Tseng, Ph.D., tested Ab8 using live SARS-CoV-2 virus.

With those results in hand, Ralph Baric, Ph.D., and his UNC colleagues tested Ab8 at varying concentrations in mice using a modified version of SARS-CoV-2.

Ab8 also was effective in treating and preventing SARS-CoV-2 infection in hamsters, as evaluated by Darryl Falzarano, Ph.D., and colleagues at the University of Saskatchewan.

Sriram Subramaniam, Ph.D., and his colleagues at the University of British Columbia uncovered the unique way Ab8 neutralizes the virus so effectively by using sophisticated electron microscopic techniques.

Reference: “High potency of a bivalent human VH domain in SARS-CoV-2 animal models” by Wei Li, Alexandra Schäfer, Swarali S.

Additional co-lead authors of this research are Xianglei Liu, M.D., Ph.D., of Pitt; Alexandra Schäfer, Ph.D., and David R.

Martinez, Ph.D., both of the University of North Carolina at Chapel Hill; and Swarali S.

Additional authors are Chuan Chen, Ph.D., Zehua Sun, Ph.D., Liyoung Zhang, Ph.D., all of Pitt; Sarah R.

Leist, Ph.D., of the University of North Carolina at Chapel Hill; Aleksandra Drelich, Ph.D., of the University of Texas Medical Branch; Marcin L.

Srivastava, Ph.D., and Xing Zhu, Ph.D., all of the University of British Columbia