Pterostilbene effectively inhibits influenza A virus infection by promoting the type I interferon production |
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| Affiliation: | 1. Department of Pharmacy, Guangdong Second Provincial General Hospital, No.466 Middle Xingang Road, Guangzhou, 510317, China;2. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, No. 1838 Shatai South Road, Baiyun District, Guangzhou, 510515, China;3. Department of Pharmacy, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, No.23 Haipang Street, North Street, Jiangmen, 529030, China;1. Laboratório de Entomologia I, Fiocruz Rondônia – Fundação Oswaldo Cruz, Lagoa, 76812-245, Porto Velho, Rondônia State, Brazil;2. Programa de Pós-Graduação em Biologia Experimental – PGBIOEXP, Fundação Universidade Federal de Rondônia – UNIR, BR-364, km 9.5, 76801-059, Porto Velho, Rondônia State, Brazil;3. Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane – Fiocruz Amazônia, Adrianópolis, 69057-070, Manaus, Amazonas State, Brazil;4. Programa de Pós-Graduação em Biologia Celular e Molecular, Instituto Oswaldo Cruz, Fiocruz, Manguinhos, 21040-360, Rio de Janeiro State, Brazil;5. Programa de Pós-Graduação em Biologia da Interação Patógeno-Hospedeiro, Instituto Leônidas e Maria Deane – Fiocruz Amazônia, Adrianópolis, 69057-070, Manaus, Amazonas State, Brazil;6. Laboratório de Virologia Molecular, Fiocruz Rondônia – Fundação Oswaldo Cruz, Lagoa, 76812-245, Porto Velho, Rondônia State, Brazil;7. Instituto Nacional de Epidemiologia da Amazônia Ocidental – INCT-EpiAmO, Lagoa, 76812-245, Porto Velho, Rondônia State, Brazil;1. Division of Pharmacy Practice and Administration, University of Missouri-Kansas City School of Pharmacy, Kansas City, Missouri, USA;2. Department of Pharmacy, Centerpoint Medical Center, Independence, Missouri, USA;1. Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu, China;2. Institute of Oceanology and Marine Fisheries, Nantong, 226007, Jiangsu, China;3. Guangxi Key Laboratory for Polysaccharide Materials and Modifications, School of Marine Sciences and Biotechnology, Guangxi University for Nationalities, Nanning, 530008, Guangxi, China;1. Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, United States;2. Animal Resource Program, Atrium Health Wake Forest Baptist, Winston Salem, NC, United States;3. Department of Comparative Medicine, Worldwide Research, Development, and Medical, Pfizer, Cambridge, MA, United States;4. Novartis Institutes for BioMedical Research, Cambridge, MA, United States;5. Merck Research Laboratories, Merck, South San Francisco, CA, United States;6. Department of Medicine, Columbia University, New York, NY, United States;7. Division of Neonatology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, United States;8. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States;1. Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China;2. Infectious Diseases Institute, Guangzhou Eighth People''s Hospital, Guangdong, China;3. School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, China;1. Department of Parasitology, Federal University of Minas Gerais, Belo Horizonte 31270901, Brazil;2. Department of Foods, Pharmacy Faculty, Federal University of Minas Gerais, Belo Horizonte 31515200, Brazil |
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| Abstract: | With the prevalence of novel strains and drug-resistant influenza viruses, there is an urgent need to develop effective and low-toxicity anti-influenza therapeutics. Regulation of the type I interferon antiviral response is considered an attractive therapeutic strategy for viral infection. Pterostilbene, a 3,5-dimethoxy analog of resveratrol, is known for its remarkable pharmacological activity. Here, we found that pterostilbene effectively inhibited influenza A virus infection and mainly affected the late stages of viral replication. A mechanistic study showed that the antiviral activity of pterostilbene might promote the induction of antiviral type I interferon and expression of its downstream interferon-stimulated genes during viral infection. The same effect of pterostilbene was also observed in the condition of polyinosinic-polycytidylic acid (poly I:C) transfection. Further study showed that pterostilbene interacted with influenza non-structural 1 (NS1) protein, inhibited ubiquitination mediated degradation of RIG-I and activated the downstream antiviral pathway, orchestrating an antiviral state against influenza virus in the cell. Taken together, pterostilbene could be a promising anti-influenza agent for future antiviral drug exploitation and compounds with similar structures may provide new options for the development of novel inhibitors against influenza A virus (IAV). |
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| Keywords: | Pterostilbene Influenza A virus Type I interferon NS1 RIG-I |
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