A small-molecule fusion inhibitor of influenza virus is orally active in mice-Reference-Cited by-同舟云学术

A small-molecule fusion inhibitor of influenza virus is orally active in mice

Published:2019-03-08 Issue:6431 Volume:363 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

van Dongen Maria J. P.¹²^ORCID,Kadam Rameshwar U.³^ORCID,Juraszek Jarek¹^ORCID,Lawson Edward⁴^ORCID,Brandenburg Boerries¹⁵^ORCID,Schmitz Frederike¹^ORCID,Schepens Wim B. G.²^ORCID,Stoops Bart²^ORCID,van Diepen Harry A.¹^ORCID,Jongeneelen Mandy¹⁵,Tang Chan¹⁵^ORCID,Vermond Jan¹^ORCID,van Eijgen-Obregoso Real Alida¹,Blokland Sven¹⁵,Garg Divita⁶,Yu Wenli³,Goutier Wouter¹^ORCID,Lanckacker Ellen⁷^ORCID,Klap Jaco M.¹^ORCID,Peeters Daniëlle C. G.²,Wu Jin⁷^ORCID,Buyck Christophe²^ORCID,Jonckers Tim H. M.⁷,Roymans Dirk⁷^ORCID,Roevens Peter²,Vogels Ronald¹⁵,Koudstaal Wouter¹,Friesen Robert H. E.¹,Raboisson Pierre⁷,Dhanak Dashyant²⁴,Goudsmit Jaap¹⁸,Wilson Ian A.³⁹^ORCID

Affiliation:

1. Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Archimedesweg 6, Leiden, Netherlands.

2. Discovery Sciences, Janssen Research & Development, Turnhoutseweg 30, Beerse, Belgium.

3. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.

4. Discovery Sciences, Janssen Research & Development, 1400 McKean Rd., Spring House, PA, USA.

5. Janssen Infectious Diseases and Vaccines, Janssen Research & Development, Archimedesweg 4-6, Leiden, Netherlands.

6. Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.

7. Janssen Infectious Diseases and Vaccines, Janssen Research & Discovery, Turnhoutseweg 30, Beerse, Belgium.

8. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

9. The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA.

Abstract

A small molecule that targets influenza Many of us rely on seasonal vaccines for protection against influenza and are only too aware of their limited breadth. Broadly neutralizing antibodies (bnAbs) that target the conserved hemagglutinin (HA) stem of the influenza virus provide hope for the development of universal vaccines and are being evaluated in clinical trials. Van Dongen et al. selected and optimized a small-molecule lead compound that recapitulates key interactions of the bnAb with HA. Like the bnAb, the compound inhibited viral fusion in the endosomes of target cells. The compound protected mice from influenza after oral administration and neutralized virus infection in a 3D cell culture of human bronchial epithelial cells. Science , this issue p. eaar6221

Funder

National Institutes of Health

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference60 articles.

1. World Health Organization (WHO) WHO influenza (seasonal) fact sheet (2018); www.who.int/en/news-room/fact-sheets/detail/influenza-(seasonal).

2. Antiviral Therapy for Influenza

3. Broadly Neutralizing Antibodies Present New Prospects to Counter Highly Antigenically Diverse Viruses

4. Implications of broadly neutralizing antibodies in the development of a universal influenza vaccine

5. Human Monoclonal Antibodies Broadly Neutralizing against Influenza B Virus

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