"There's still much work to be done to make this antibody-based drug available to patients to treat COVID-19 but it's an exciting and promising advance as we will work on multiple strategies to end this pandemic", said Dr. Steven Shapiro, UPMC's chief medical and scientific officer.
The UPMC and Pitt researchers are collaborating with scientists at the University of North Carolina, University of Texas Medical Branch, the University of British Columbia and University of Saskatchewan. The drug is seen as a potential preventative against SARS-CoV-2.
They said the molecule doesn't bind to human cells, which they called "a good sign it won't have negative side-effects in people". The size also helps in administering the drug by alternative routes, such as inhalation.
"We have already discovered that one treatment, dexamethasone, benefits COVID-19 patients, but the death rate remains too high so we must keep searching for others". After these discoveries, his team identified potent antibodies against many other infectious diseases, including those caused by the Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV), dengue, Hendra and Nipah viruses. Next, to increase the VH ab8 avidity and extend its in vivo half-life, it was converted to a bivalent antibody domain by fusion to the human IgG1 Fc (VH-Fc ab8).
"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. REGN-COV2 is now being studied in two Phase 2/3 clinical trials for the treatment of COVID-19 and in a Phase 3 trial for the prevention of COVID-19 in household contacts of infected individuals. This corresponds to the specificity of an antibody molecule towards a particular virus. They found that ab8 blocked the virus from entering cells, outperforming the angiotensin converting enzyme 2 (ACE2) receptor for binding to the RBD.
With those results in hand, a team at UNC tested Ab8 at varying concentrations in mice using a modified version of SARS-CoV-2.
Dr Dimiter Dimitrov, senior author of the paper and director of University of Pittsburgh's Center for Antibody Therapeutics, was one of the first to discover neutralising antibodies for the original Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2003. In mice trials, those treated with Ab8 had 10-fold less of the amount of infectious virus compared to those that were untreated.
Mellors says, "The COVID-19 pandemic is a global challenge facing humanity, but biomedical science and human ingenuity are likely to overcome it..."