Tiny biologic drug shows promise in animal model to fight COVID-19

Neutral monoclonal antibodies are promising tools in the fight against COVID-19, but their large size usually limits the administration route to intravenous infusion.

Now, a research team led by scientists from the University of Pittsburgh School of Medicine has identified an antibody component that is 10 times smaller than a full-size antibody. In mice and hamsters, the novel behind COSID-19 was found to be highly effective in preventing and treating the coronovirus SARS-CoV-2, according to published results on the cell.

Some members of the team have formed a startup called Abound Bio with the goal of bringing the candidate, dubbed AB8, into clinical trials, possibly as a respiratory drug against COVID-19.

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“A8 not only has potential as a therapy for COVID-19, but it can also be used to protect people from SARS-COV-2 infection,” co-author John Mellors, MD, a Said in the statement. “Large-sized antibodies have worked against other infectious diseases and have been well tolerated, leading us to hope that this may be an effective treatment for patients with COVID-19 and for the preservation of those Those who have never had an infection and are not immune. ”

Researchers who began screening a library of nearly 100 billion antibody fragments to search for candidates that bind tightly to spike proteins on the surface of SARS-CoV-2, which the virus uses to enter and infect human cells Huh.

The chosen molecule is the variable domain of a heavy chain of immunoglobulins, a type of antibody. A specific antibody consists of two heavy chains and two light chains. The heavy chain variable domain is required for binding with the antigen.

Ab8 was created by fusing variable, heavy chain domains with part of the immunoglobulin tail region from which it performs immune functions but doing so with one molecule is about half the size of a complete immunoglobulin.

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Researchers wrote in the study that the small size “may improve therapeutic efficacy for infectious diseases, such as COVID-19, due to greater penetration into sites of infection.” In addition, because it efficiently penetrates the tissue, it can be delivered directly via inhalation, another benefit for treating respiratory disease, he added.

Ab8 completely neutralized SARS-CoV-2 in laboratory dishes. In an adaptive mouse model, animals receiving Ab8 were then challenged with SARS-CoV-2. Researchers reported that the drug effectively inhibited the virus in lung tissue in a dose-dependent manner, tenfold significant reduction of virus titer, even at 2 mg / kg compared to untreated controls. At low doses.

The team tested the drug’s effect in hamsters, which were recently shown to better represent the clinical signatures of COVID-19. Ab8 treatment successfully reduced viral load in the lungs, as well as viral shedding from the nose and mouth, in both preventive and therapeutic settings. And the hamsters who received the drug showed less severe pneumonia than the control animals.

What’s more, Ab8 does not appear to bind human cells, a good sign that it will not have negative side effects in people, the scientists argued.

Drugs with alternative administration routes may be valued in addition to COVID-19 treatments and the first wave of vaccines. Another University of Pittsburgh team has recently developed a vaccine candidate, dubbed Pitkovac, which performs a vaccination through a Band-Aid-like patch containing microneedles made from sugar.

Several neutralizing antibodies against SARS-CoV-2 are already in clinical trials. The Pitt-led team believes that the small-sized A8, thanks to its increased proliferation through the tissues, may be given as a inhaled drug rather than intravenously like most antibodies in development, possibly Provides a more convenient option.