A universal dual mechanism immunotherapy for the treatment of influenza virus infections

Xin Liu, Boning Zhang, Yingcai Wang, Hanan S. Haymour, Fenghua Zhang, Le-cun Xu, Madduri Srinivasarao and Philip S. Low ()
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Xin Liu: Purdue University
Boning Zhang: Purdue University
Yingcai Wang: Purdue University
Hanan S. Haymour: Purdue University
Fenghua Zhang: Purdue University
Le-cun Xu: Endocyte Inc.
Madduri Srinivasarao: Purdue University
Philip S. Low: Purdue University

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Seasonal influenza epidemics lead to 3–5 million severe infections and 290,000–650,000 annual global deaths. With deaths from the 1918 influenza pandemic estimated at >50,000,000 and future pandemics anticipated, the need for a potent influenza treatment is critical. In this study, we design and synthesize a bifunctional small molecule by conjugating the neuraminidase inhibitor, zanamivir, with the highly immunogenic hapten, dinitrophenyl (DNP), which specifically targets the surface of free virus and viral-infected cells. We show that this leads to simultaneous inhibition of virus release, and immune-mediated elimination of both free virus and virus-infected cells. Intranasal or intraperitoneal administration of a single dose of drug to mice infected with 100x MLD50 virus is shown to eradicate advanced infections from representative strains of both influenza A and B viruses. Since treatments of severe infections remain effective up to three days post lethal inoculation, our approach may successfully treat infections refractory to current therapies.

Date: 2020
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DOI: 10.1038/s41467-020-19386-5

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