To address the challenge of viral mutations that evade existing vaccines and antibody treatments, they developed the broad-spectrum antiviral Adaptive Multi-Epitope Targeting and Avidity-Enhanced (AMETA) platform. Using engineered nanobodies to target multiple stable regions of the virus that are less likely to mutate, AMETA enhances binding strength to provide lasting and robust protection against SARS-CoV-2 and other rapidly evolving pathogens.
Since the onset of the COVID-19 pandemic, continuous viral mutations have led to the gradual inefficacy of existing vaccines and antibodies. To tackle this issue, Dr Shi Yi’s team at Mount Sinai developed the AMETA platform. Dr Shi Yi said, ‘Viral mutation escape is a major challenge; existing antibodies typically bind to only one or two sites, quickly losing effectiveness, and frequent updates incur high research costs. AMETA targets multiple conserved regions and enhances binding strength, significantly increasing resistance to viral escape, showing promise as a long-term solution against rapidly mutating pathogens.’
AMETA’s unique design incorporates bispecific nanobodies and a human IgM framework, creating an antiviral structure with 20 binding sites that can target multiple conserved epitopes simultaneously, achieving up to a million-fold increase in antiviral efficacy compared to traditional single-target nanobodies. Laboratory tests and preclinical trials in mice demonstrated that AMETA is highly effective against various SARS-CoV-2 variants, including the highly mutated Omicron subvariants and the SARS-CoV virus.
They collaborated with scientists in NDM, such as Professor Zhang Peijun, Professor of Structural Biology and Wellcome Trust Investigator at the Division of Structural Biology and CAMS Oxford Institute Principal Investigator, using cryo-electron tomography to analyse AMETA's structure and mechanism of action. Their research showed that AMETA not only aggregates and locks viral particles but also disrupts spike structures, rendering the virus incapable of infection.
Professor Zhang said: ‘With cryo-tomography, we observed AMETA neutralising the virus in an unprecedented manner. AMETA’s mechanism makes it a potent tool against other rapidly mutating pathogens, such as HIV and potential pandemic influenza viruses.’
Read the full paper on the Cell website: https://doi.org/10.1016/j.cell.2024.09.043