Pitna V Lee, PhD, demonstrates a step in the process of obtaining a potential drug against COVID-19. Credit: UPMC
Scientists at the University of Pittsburgh School of Medicine have isolated the smallest biological molecules to date that are completely and utterly neutral. SARS-CoV-2 The virus, which is the cause COVID-19. This antibody component, which is 10 times smaller than a full-size antibody, is known for its potential use as a therapeutic and prophylactic against SARS-CoV-2 – a drug known as AB8.
Researchers have reported in the journal Today (September 14, 2020) Cell AB8 is very effective in preventing and treating SARS-Co-2 infections in mice and hamsters. Its small size increases the likelihood of the virus spreading to tissues for better inactivation, but also makes it possible to administer the drug through alternative routes, including inhalation. Importantly, it cannot bind to human cells – a good sign that it will not cause negative side effects in humans.
AB8 was evaluated by the University of North Carolina at Chapel Hill (UNC) and the University of Texas Medical Branch (UTMB) along with Galveston, as well as the University of British Columbia and the University of Saskatchewan.
“AB8 not only has the potential to cure Covid-19, but can also be used to prevent people from getting SARS-Co-2 infections,” said John Mellors, M-author, head of the infectious diseases department at UPMC. And Pitt. “Large-sized antibodies work against other infectious diseases and are well tolerated. We hope they may be an effective treatment for patients with COVID-19 who have never been infected and have no immunity.”
John Mellors, MD, head of infectious diseases at UPMC and the University of Pittsburgh, discusses the scientific breakthrough that is a major step toward a potential drug for the treatment and prevention of Covid-19. Credit: UPMC
The small antibody component is a variant of the immunoglobulin, the heavy chain (VH) domain, 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-Co-2 spike protein as a bait. AB8 is formed when the VH domain immunoglobulin is attached to part of the tail region, adding the immune function of a full-size antibody without bulk.
Newly formed UPMC-backed company Abound Bio has obtained AB8 license for worldwide development.
Dimitar Dimitrov, Ph.D. Credit: University of Pittsburgh
Dimitar Dimitrov, PhD, senior author Cell Pitts was the first person to discover neutral antibodies to the original SARS coronavirus in 2003, the publication and director of the Center for Antibody Therapeutics. Over the years, his team discovered powerful antibodies against many other infectious diseases, including MERS-CV. , Dengue, hendra and nipah viruses. Antibodies against Hendra and Nipah viruses in humans have been evaluated and approved for clinical use on compassionate basis in clinical Australia.
Clinical trials are testing consistently Plasma – which includes antibodies from people who already have Covid-19 as a treatment for people fighting the infection, but not enough plasma for those who need it, and it is not proven to work.
That is why Dimitrov and his team decided to isolate the gene for one or more antibodies that block the SARS-Covi-2 virus, allowing for large-scale production. In February, V Lee, Ph.D., assistant director and co-lead author of the research at the Pitts Center for Therapeutic Antibodies, began investigating large libraries of antibody components created using human blood samples and found several therapeutic antibody candidates, including AB8. , In record time.
ABT was then tested using the live SARS-Co-2 virus, led by UTMB’s Center for Biodefense and Emerging Diseases and Galveston National Laboratory, Chen-T Kent Tseng, Ph.D. At very low concentrations, AB8 prevented the virus from entering the cells. With those results in hand, Ralph Barrick, Ph.D., and his U.N.C. The colleagues tested AB8 at different concentrations in mice using a modified version of SARS-COV-2. Even at the lowest dose, AB8 reduced the amount of infectious virus in those rats by 10 times compared to their untreated counterparts. AB8 was also effective in treating and preventing SARS-Cavi-2 infection in hamsters, as evaluated by Daryl Falzarano, Ph.D., and colleagues at the University of Saskatchewan. Shriram Subramaniam, Ph.D., and his colleagues at the University of British Columbia discovered a unique way to make the AB8 virus more effective using sophisticated electron microscopic techniques.
“The Kovid-1P epidemic is a global challenge facing humanity, but biomedical science and human ingenuity can overcome it,” said Mallor, the prestigious chair of medicine for the global eradication of HIV and AIDS at Pete. . “We hope that the antibodies we have discovered will contribute to that victory.”
References: V Lee, Alexandra Schaefer, Swarali S. Kulkarni, Jiangeli Liu, David R. Martinez, Chuan Chen, Zhuhua Sun, Sara R. List by “The High Power of Bilingual Human VH Domains in SARS-Cavi-2 Animal Models”, Alexandra Dralich, Leong Zhang, Markin L. Ra Ra, Alison Berezuk, Sagar Chittori, Caroline Leopold, Patience Mannar, Shanti S. Srivastava, Xing Xu, Eric C. Peterson, Chen-te Tseng, John W. Malors, Daryl Falzarano, Shriram Subramaniam, Ralph S. Barrick and Demeter S. Dimitrov, Accessed 31 August Gust 2020, Cell.
DOI: 10.1016 / j.cell.2020.09.007
Additional co-lead authors of this research are Pete’s MIN, Ph.D., Xiangli Liu; Alexandra Schoffer, Ph.D., and David R. Martinez, Ph.D., both of Paul Hill University of North Carolina; And Swarali S. of Saskatchewan University. Kulkarni, M.Sc. Additional authors are Chuan Chen, Ph.D., Zhehua Sun, Ph.D., Liaong Zhang, Ph.D., all Pete; Sarah R. List, Ph.D., University of North Carolina at Chapel Hill; Alexandra Drelich, Ph.D., of the University of Texas Medical Branch. Markin L. Ura, Ph.D., and Eric Peterson, MS, both Abundant Bio; And Alison Berezuk, Ph.D., Sagar Chittori, Ph.D., Caroline Leopold, Ph.D., Dhiraj Mannar, B.Sc., Shanti S. Srivastava, Ph.D., and Xing Xu, Ph.D. ., University of British Columbia.
The research was funded by F32 AI152296, T32 AI007151, AI132178, AI108197 and P30CA016086, as well as national health organizations by UPMC; Burrows Welcome Fund; Canada Excellence Research Chair Award; Genome BC, Canada; Canadian institutes for health research; And the Canadian Foundation for Innovation.
