PMID- 34372556
OWN - NLM
STAT- MEDLINE
DCOM- 20210916
LR  - 20210916
IS  - 1999-4915 (Electronic)
IS  - 1999-4915 (Linking)
VI  - 13
IP  - 7
DP  - 2021 Jul 13
TI  - Antiviral Activity of Chrysin against Influenza Virus Replication via Inhibition 
      of Autophagy.
LID - 10.3390/v13071350 [doi]
LID - 1350
AB  - Influenza viruses cause respiratory infections in humans and animals, which have 
      high morbidity and mortality rates. Although several drugs that inhibit viral 
      neuraminidase are used to treat influenza infections, the emergence of resistant 
      viruses necessitates the urgent development of new antiviral drugs. Chrysin 
      (5,7-dihydroxyflavone) is a natural flavonoid that exhibits antiviral activity 
      against enterovirus 71 (EV71) by inhibiting viral 3C protease activity. In this 
      study, we evaluated the antiviral activity of chrysin against influenza A/Puerto 
      Rico/8/34 (A/PR/8). Chrysin significantly inhibited A/PR/8-mediated cell death 
      and the replication of A/PR/8 at concentrations up to 2 muM. Viral hemagglutinin 
      expression was also markedly decreased by the chrysin treatment in 
      A/PR/8-infected cells. Through the time course experiment and time-of-addition 
      assay, we found that chrysin inhibited viral infection at the early stages of the 
      replication cycle. Additionally, the nucleoprotein expression of A/PR/8 in A549 
      cells was reduced upon treatment with chrysin. Regarding the mechanism of action, 
      we found that chrysin inhibited autophagy activation by increasing the 
      phosphorylation of mammalian target of rapamycin (mTOR). We also confirmed a 
      decrease in LC3B expression and LC3-positive puncta levels in A/PR/8-infected 
      cells. These results suggest that chrysin exhibits antiviral activity by 
      activating mTOR and inhibiting autophagy to inhibit the replication of A/PR/8 in 
      the early stages of infection.
FAU - Kim, Seong-Ryeol
AU  - Kim SR
AD  - Department of Pharmacy, Kangwon National University, Chuncheon 24341, Korea.
FAU - Jeong, Myeong-Seon
AU  - Jeong MS
AD  - Chuncheon Center, Korea Basic Science Institute (KBSI), Chuncheon 24341, Korea.
FAU - Mun, Seo-Hyeon
AU  - Mun SH
AD  - Department of Pharmacy, Kangwon National University, Chuncheon 24341, Korea.
FAU - Cho, Jaewon
AU  - Cho J
AD  - Department of Pharmacy, Kangwon National University, Chuncheon 24341, Korea.
FAU - Seo, Min-Duk
AU  - Seo MD
AD  - College of Pharmacy and Research Institute of Pharmaceutical Science and 
      Technology (RIPST), Ajou University, Suwon 16499, Korea.
FAU - Kim, Hyoungsu
AU  - Kim H
AUID- ORCID: 0000-0002-2774-8727
AD  - College of Pharmacy and Research Institute of Pharmaceutical Science and 
      Technology (RIPST), Ajou University, Suwon 16499, Korea.
FAU - Lee, Jooeun
AU  - Lee J
AD  - Chuncheon Center, Korea Basic Science Institute (KBSI), Chuncheon 24341, Korea.
FAU - Song, Jae-Hyoung
AU  - Song JH
AD  - Department of Pharmacy, Kangwon National University, Chuncheon 24341, Korea.
AD  - Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon 
      24341, Korea.
FAU - Ko, Hyun-Jeong
AU  - Ko HJ
AD  - Department of Pharmacy, Kangwon National University, Chuncheon 24341, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210713
PL  - Switzerland
TA  - Viruses
JT  - Viruses
JID - 101509722
RN  - 0 (Antiviral Agents)
RN  - 0 (Flavonoids)
RN  - 0 (Viral Proteins)
RN  - 3CN01F5ZJ5 (chrysin)
RN  - EC 3.2.1.18 (Neuraminidase)
SB  - IM
MH  - A549 Cells
MH  - Animals
MH  - Antiviral Agents/pharmacology
MH  - Autophagy/drug effects
MH  - Dogs
MH  - Flavonoids/metabolism/*pharmacology
MH  - Humans
MH  - Influenza A virus/*drug effects/pathogenicity
MH  - Influenza, Human/drug therapy/metabolism
MH  - Madin Darby Canine Kidney Cells
MH  - Neuraminidase/metabolism
MH  - Viral Proteins/metabolism
MH  - Virus Replication/*drug effects
PMC - PMC8310364
OTO - NOTNLM
OT  - antiviral activity
OT  - autophagy
OT  - chrysin
OT  - influenza A/Puerto Rico/8/34
OT  - mTOR
COIS- The authors declare no conflict of interest.
EDAT- 2021/08/11 06:00
MHDA- 2021/09/18 06:00
PMCR- 2021/07/13
CRDT- 2021/08/10 01:05
PHST- 2021/06/08 00:00 [received]
PHST- 2021/07/07 00:00 [revised]
PHST- 2021/07/09 00:00 [accepted]
PHST- 2021/08/10 01:05 [entrez]
PHST- 2021/08/11 06:00 [pubmed]
PHST- 2021/09/18 06:00 [medline]
PHST- 2021/07/13 00:00 [pmc-release]
AID - v13071350 [pii]
AID - viruses-13-01350 [pii]
AID - 10.3390/v13071350 [doi]
PST - epublish
SO  - Viruses. 2021 Jul 13;13(7):1350. doi: 10.3390/v13071350.