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

• Published in: Nature communications 2020-11, Vol.11 (1), p.5597-5597, Article 5597
• Main Authors: Liu, Xin, Zhang, Boning, Wang, Yingcai, Haymour, Hanan S., Zhang, Fenghua, Xu, Le-cun, Srinivasarao, Madduri, Low, Philip S.
• Format: Article
• Language: English
• Subjects: 13/1; 13/106; 13/31; 14/1; 14/19; 14/34; 38; 59; 631/154/152; 631/250/251; 631/326/596/1578; 64; 64/60; Antiviral agents; Chemical synthesis; Epidemics; Exo-a-sialidase; Fatalities; Humanities and Social Sciences; Immune system; Immunogenicity; Immunotherapy; Infections; Influenza; Influenza A; Inoculation; multidisciplinary; Pandemics; Science; Science (multidisciplinary); Viral infections; Viruses; Zanamivir
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-19386-5

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 MLD 50 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. In this study, the authors combine an anti-viral drug and immune system inducer to treat influenza A and B viral infections in vitro and in vivo. They show that the compound outperforms zanamivir alone as it is still able to clear infection three days post infection, and it can be administered via different routes without reduced efficacy.