PMID- 33176871
OWN - NLM
STAT- MEDLINE
DCOM- 20210614
LR  - 20210614
IS  - 1297-9716 (Electronic)
IS  - 0928-4249 (Print)
IS  - 0928-4249 (Linking)
VI  - 51
IP  - 1
DP  - 2020 Nov 11
TI  - Tomatidine inhibits porcine epidemic diarrhea virus replication by targeting 3CL 
      protease.
PG  - 136
LID - 10.1186/s13567-020-00865-y [doi]
LID - 136
AB  - Porcine epidemic diarrhea virus (PEDV) causes lethal diarrhea in suckling 
      piglets, leading to severe economic losses worldwide. There is an urgent need to 
      find new therapeutic methods to prevent and control PEDV. Not only is there a 
      shortage of commercial anti-PEDV drugs, but available commercial vaccines fail to 
      protect against highly virulent PEDV variants. We screened an FDA-approved 
      library of 911 natural products and found that tomatidine, a steroidal alkaloid 
      extracted from the skin and leaves of tomatoes, demonstrates significant 
      inhibition of PEDV replication in Vero and IPEC-J2 cells in vitro. Molecular 
      docking and molecular dynamics analysis predicted interactions between tomatidine 
      and the active pocket of PEDV 3CL protease, which were confirmed by fluorescence 
      spectroscopy and isothermal titration calorimetry (ITC). The inhibiting effect of 
      tomatidine on 3CL protease was determined using cleavage visualization and FRET 
      assay. Tomatidine-mediated blocking of 3CL protease activity in PEDV-infected 
      cells was examined by western blot detection of the viral polyprotein in 
      PEDV-infected cells. It indicates that tomatidine inhibits PEDV replication 
      mainly by targeting 3CL protease. In addition, tomatidine also has antiviral 
      activity against transmissible gastroenteritis virus (TGEV), porcine reproductive 
      and respiratory syndrome virus (PRRSV), encephalo myocarditis virus (EMCV) and 
      seneca virus A (SVA) in vitro. These results may be helpful in developing a new 
      prophylactic and therapeutic strategy against PEDV and other swine disease 
      infections.
FAU - Wang, Pengcheng
AU  - Wang P
AD  - Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of 
      Agriculture, MOE International Joint Collaborative Research Laboratory for Animal 
      Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural 
      University, Nanjing, 210095, China.
FAU - Bai, Juan
AU  - Bai J
AD  - Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of 
      Agriculture, MOE International Joint Collaborative Research Laboratory for Animal 
      Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural 
      University, Nanjing, 210095, China.
FAU - Liu, Xuewei
AU  - Liu X
AD  - Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of 
      Agriculture, MOE International Joint Collaborative Research Laboratory for Animal 
      Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural 
      University, Nanjing, 210095, China.
FAU - Wang, Mi
AU  - Wang M
AD  - Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of 
      Agriculture, MOE International Joint Collaborative Research Laboratory for Animal 
      Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural 
      University, Nanjing, 210095, China.
FAU - Wang, Xianwei
AU  - Wang X
AD  - Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of 
      Agriculture, MOE International Joint Collaborative Research Laboratory for Animal 
      Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural 
      University, Nanjing, 210095, China. xwwang@njau.edu.cn.
AD  - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal 
      Infectious Diseases and Zoonoses, Yangzhou, China. xwwang@njau.edu.cn.
FAU - Jiang, Ping
AU  - Jiang P
AUID- ORCID: 0000-0002-0918-0082
AD  - Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of 
      Agriculture, MOE International Joint Collaborative Research Laboratory for Animal 
      Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural 
      University, Nanjing, 210095, China. jiangp@njau.edu.cn.
AD  - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal 
      Infectious Diseases and Zoonoses, Yangzhou, China. jiangp@njau.edu.cn.
LA  - eng
GR  - CARS-35/the Ministry of Agriculture for Swine Disease Control/
GR  - 2018YFD0500803/the National Key Program of Research and Development of China/
PT  - Journal Article
DEP - 20201111
PL  - England
TA  - Vet Res
JT  - Veterinary research
JID - 9309551
RN  - 0 (Antiviral Agents)
RN  - 0 (Plant Extracts)
RN  - 0 (Viral Proteins)
RN  - 2B73S48786 (tomatidine)
RN  - 31U6547O08 (Tomatine)
RN  - EC 3.4.- (Peptide Hydrolases)
SB  - IM
MH  - Antiviral Agents/chemistry/*pharmacology
MH  - Peptide Hydrolases/metabolism
MH  - Plant Extracts/chemistry/pharmacology
MH  - Porcine epidemic diarrhea virus/drug effects/enzymology/*physiology
MH  - Tomatine/*analogs & derivatives/chemistry/pharmacology
MH  - Viral Proteins/*metabolism
MH  - Virus Replication/*drug effects/physiology
PMC - PMC7656508
OTO - NOTNLM
OT  - 3CL protease
OT  - PEDV replication
OT  - tomatidine
COIS- None of the authors have any possible conflicts of interest.
EDAT- 2020/11/13 06:00
MHDA- 2021/06/16 06:00
PMCR- 2020/11/11
CRDT- 2020/11/12 05:31
PHST- 2020/08/29 00:00 [received]
PHST- 2020/10/26 00:00 [accepted]
PHST- 2020/11/12 05:31 [entrez]
PHST- 2020/11/13 06:00 [pubmed]
PHST- 2021/06/16 06:00 [medline]
PHST- 2020/11/11 00:00 [pmc-release]
AID - 10.1186/s13567-020-00865-y [pii]
AID - 865 [pii]
AID - 10.1186/s13567-020-00865-y [doi]
PST - epublish
SO  - Vet Res. 2020 Nov 11;51(1):136. doi: 10.1186/s13567-020-00865-y.