Pan-coronavirus antiviral activity and mechanism of molecularly engineered banana lectin

Background

New SARS-CoV-2 variants and other coronaviruses are likely to emerge in the future. Some of these may develop resistance to existing antivirals. Thus, ‘pan-coronavirus’ antivirals are urgently needed to prepare for these emerging threats. The research team investigated the antiviral effect of the molecularly engineered banana lectin ‘H84T-BanLec’ against SARS-CoV-2 and other known human-pathogenic coronaviruses in a series of cell line, human ex vivo lung tissue and animal models. The team found that H84T-BanLec potently inhibits all of the coronaviruses tested through binding to multiple spike mannose sites with high affinity to inhibit viral entry into host cells. This unique antiviral mechanism of H84T-BanLec makes it difficult for the viruses to develop resistance and allows H84T-BanLec to be a potential ‘pan-coronavirus’ antiviral for the current COVID-19 and future coronavirus pandemics.

Research methodology and findings

BanLec is a lectin from the jacalin-related lectin family isolated from bananas. The molecularly engineered H84T-BanLec possesses preserved antiviral activity and reduced mitogenicity. H84T-BanLec potently inhibits SARS-CoV-2 and its variants (including Omicron), MERS-CoV, SARS-CoV-1, HCoV-OC43, and HCoV-229E in cell lines. In the human ex vivo lung tissue culture model, H84T-BanLec inhibits MERS-CoV at nanomolar concentrations. H84T-BanLec significantly increased the survival rate of human DPP4-knockin mice infected with MERS-CoV. Importantly, intranasal administration was similarly effective as intraperitoneal administration of H84T-BanLec in the golden Syrian hamster model of COVID-19. Structural analyses with high-speed atomic force microscopy and single-molecular force spectroscopy demonstrated the binding of H84T-BanLec to multiple SARS-CoV-2 spike mannose sites with high affinity. The multiple H84T-BanLec binding sites on spike likely account for the drug compound’s broad-spectrum antiviral activity and the lack of resistant mutants.

Significance of the study

The study shows that H84T-BanLec is highly active against not only SARS-CoV-2 and its variants, but also other known human-pathogenic coronaviruses. The unique mechanism of H84T-BanLec makes it a potential ‘pan-coronavirus’ antiviral drug compound that is not likely to become ineffective against new SARS-CoV-2 variants and novel coronaviruses that are likely to emerge in the future. Importantly, as H84T-BanLec is known to be also active against other viruses such as influenza viruses, intranasal administration of H84T-BanLec may become an especially useful for countermeasure for seasonal outbreaks of respiratory viruses.

About the research team

Dr Jasper Chan Fuk-woo, Clinical Associate Professor; Dr Yuan Shuofeng, Assistant Professor; Dr Chu Hin, Assistant Professor; Department of Microbiology, School of Clinical Medicine, HKUMed; and Dr Yoo Jin Oh, Johannes Kepler University Linz are co-first authors of this study.

Professor Yuen Kwok-yung, Henry Fok Professor in Infectious Diseases, Chair Professor of Department of Microbiology, School of Clinical Medicine, HKUMed, Co-Director of the State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong and Academician of the Chinese Academy of Engineering; Professor David Markovitz, University of Michigan; and Professor Peter Hinterdorfer, Johannes Kepler University Linz are corresponding authors of this study.

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