#Azithromycin, a 15-membered #macrolide #antibiotic, inhibits #influenza A #H1N1pdm09 virus #infection by interfering with virus internalization process (J Antibit (Tokyo), abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Antibiot (Tokyo). 2019 Jul 12. doi: 10.1038/s41429-019-0204-x. [Epub ahead of print]

Azithromycin, a 15-membered macrolide antibiotic, inhibits influenza A(H1N1)pdm09 virus infection by interfering with virus internalization process.

Tran DH1,2, Sugamata R1,2,3, Hirose T4, Suzuki S1,2,3, Noguchi Y4, Sugawara A4,5, Ito F2, Yamamoto T2, Kawachi S2,3, Akagawa KS4, Ōmura S4, Sunazuka T4, Ito N6, Mimaki M6, Suzuki K7,8,9.

Author information: 1 Department of Health Protection, Graduate School of Medicine, Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. 2 Asia International Institute of Infectious Disease Control (ADC), Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. 3 General Medical Education and Research Center (G-MEC), Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. 4 Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, Shirokane 5-9-1, Minato-ku, Tokyo, 108-8641, Japan. 5 Graduate School of Pharmaceutical Sciences, Tohoku University, Aza-Aoba 6-3, Aramaki, Aoba-ku, Sendai, 980-8578, Japan. 6 The Pediatric Department, Teikyo Hospital University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. 7 Department of Health Protection, Graduate School of Medicine, Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. suzuki-k@med.teikyo-u.ac.jp. 8 Asia International Institute of Infectious Disease Control (ADC), Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. suzuki-k@med.teikyo-u.ac.jp. 9 General Medical Education and Research Center (G-MEC), Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. suzuki-k@med.teikyo-u.ac.jp.

 

Abstract

The pandemic influenza 2009 (A(H1N1)pdm09) virus currently causes seasonal and annual epidemic outbreaks. The widespread use of anti-influenza drugs such as neuraminidase and matrix protein 2 (M2) channel inhibitors has resulted in the emergence of drug-resistant influenza viruses. In this study, we aimed to determine the anti-influenza A(H1N1)pdm09 virus activity of azithromycin, a re-positioned macrolide antibiotic with potential as a new anti-influenza candidate, and to elucidate its underlying mechanisms of action. We performed in vitro and in vivo studies to address this. Our in vitro approaches indicated that progeny virus replication was remarkably inhibited by treating viruses with azithromycin before infection; however, azithromycin administration after infection did not affect this process. We next investigated the steps inhibited by azithromycin during virus invasion. Azithromycin did not affect attachment of viruses onto the cell surface, but blocked internalization into host cells during the early phase of infection. We further demonstrated that azithromycin targeted newly budded progeny virus from the host cells and inactivated their endocytic activity. This unique inhibitory mechanism has not been observed for other anti-influenza drugs, indicating the potential activity of azithromycin before and after influenza virus infection. Considering these in vitro observations, we administered azithromycin intranasally to mice infected with A(H1N1)pdm09 virus. Single intranasal azithromycin treatment successfully reduced viral load in the lungs and relieved hypothermia, which was induced by infection. Our findings indicate the possibility that azithromycin could be an effective macrolide for the treatment of human influenza.

PMID:  31300721  DOI: 10.1038/s41429-019-0204-x

Keywords: Antibiotics; Azithromycin; Influenza A; H1N1pdm09.

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gimi69

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.

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