Researchers Identify ‘Nanobodies’ That Can Block Novel Coronavirus from Entering Human Cells

Researchers at the Karolinska Institutet (Stockholm, Sweden) have identified a small neutralizing antibody, a so-called nanobody that has the capacity to block SARS-CoV-2 from entering human cells and believe it has the potential to be developed as an antiviral treatment against COVID-19.

Nanobodies - which are fragments of antibodies that occur naturally in camelids and can be adapted for humans - offer several advantages over conventional antibodies as candidates for specific therapies. They span less than one-tenth the size of conventional antibodies and are typically easier to produce cost-effectively at scale. Critically, they can be adapted for humans with current protocols and have a proven record of inhibiting viral respiratory infections. In February, the researchers began their search for effective nanobodies by injecting an alpaca with the new coronavirus’ spike protein, which is used to enter human cells. After 60 days, blood samples from the alpaca showed a strong immune response against the spike protein. Next, the researchers cloned, enriched and analyzed nanobody sequences from the alpaca’s B cells, a type of white blood cell, to determine which nanobodies were best suited for further evaluation. They identified one, Ty1 (named after the alpaca Tyson), that efficiently neutralizes the virus by attaching itself to the part of the spike protein that binds to the receptor ACE2, which is used by SARS-CoV-2 to infect cells. This blocks the virus from slipping into the cells and thus prevents infection.

"Our results show that Ty1 can bind potently to the SARS-CoV-2 spike protein and neutralize the virus, with no detectable off-target activity,” said Ben Murrell, assistant professor in the Department of Microbiology, Tumor and Cell Biology and co-senior author of the publication. “We are now embarking on preclinical animal studies to investigate the neutralizing activity and therapeutic potential of Ty1 in vivo”

“We hope our findings can contribute to the amelioration of the COVID-19 pandemic by encouraging further examination of this nanobody as a therapeutic candidate against this viral infection,” said Gerald McInerney, corresponding author and associate professor of virology at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet.

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