Late last year, Shi and his team announced that they’d extracted tiny, but extremely powerful, SARS-CoV-2 antibody fragments from llamas, which could be fashioned into inhalable therapeutics to prevent and treat COVID-19. Since then, preclinical studies have verified that the potent nanobodies prevent and treat severe COVID-19 in hamsters, reducing virus particles in their respiratory tracts by a million-fold compared to placebo.

In this latest study, Shi partnered with Pitt structural biologists Cheng Zhang, Ph.D., and James Conway, Ph.D., as well as pharmacologists, structural biologists and biochemists at Case Western Reserve, to use high-resolution cryoelectron microscopy to observe exactly how the nanobodies interact with the SARS-CoV-2 virus to stop it from infecting cells and discover how mutations found in variants may affect nanobody interactions.

The first systematic classification of ultrapotent nanobodies reveals that the microscopic molecules work against SARS-CoV-2 in three ways. Credit: CWRU

“Cryoelectron microscopy has been demonstrated many times to be an extremely useful tool to see high-resolution structural information,” said co-senior author Wei Huang, Ph.D., research scientist in the Department of Pharmacology at the Case Western Reserve School of Medicine. “And nanobodies are versatile and stable biologics that can be used in other research, such as cancer.”

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