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

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Nat Commun


. 2020 Nov 5;11(1):5597.
doi: 10.1038/s41467-020-19386-5.
A universal dual mechanism immunotherapy for the treatment of influenza virus infections


Xin Liu ^{1 2} , Boning Zhang ^{1 2} , Yingcai Wang ^{1 2} , Hanan S Haymour ^{1 2} , Fenghua Zhang ^{1 2} , Le-Cun Xu ³ , Madduri Srinivasarao ^{1 2} , Philip S Low ^{4 5}



Affiliations

• PMID: 33154358
• DOI: 10.1038/s41467-020-19386-5

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.