PMID- 34929295
OWN - NLM
STAT- MEDLINE
DCOM- 20220120
LR  - 20221207
IS  - 1872-7913 (Electronic)
IS  - 0924-8579 (Print)
IS  - 0924-8579 (Linking)
VI  - 59
IP  - 1
DP  - 2022 Jan
TI  - Effects of simeprevir on the replication of SARS-CoV-2 in vitro and in transgenic 
      hACE2 mice.
PG  - 106499
LID - S0924-8579(21)01340-6 [pii]
LID - 10.1016/j.ijantimicag.2021.106499 [doi]
AB  - In a bid to contain the current COVID-19 (coronavirus disease 2019) pandemic, 
      various countermeasures have been applied. To date, however, there is a lack of 
      an effective drug for the treatment of COVID-19. Through molecular modelling 
      studies, simeprevir, a protease inhibitor approved for the management of 
      hepatitis C virus infection, has been predicted as a potential antiviral against 
      SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causative agent 
      of COVID-19. Here we assessed the efficacy of simeprevir against SARS-CoV-2 both 
      in vitro in Vero E6 cells and in vivo in a human angiotensin-converting enzyme 2 
      (hACE2) transgenic mouse model. The results showed that simeprevir could inhibit 
      SARS-CoV-2 replication in Vero E6 cells with a half-maximal effective 
      concentration (EC(50)) of 1.41 +/- 0.12 muM. In a transgenic hACE2 mouse model of 
      SARS-CoV-2 infection, intraperitoneal administration of simeprevir at 10 
      mg/kg/day for 3 consecutive days failed to suppress viral replication. These 
      findings collectively imply that simeprevir does not inhibit SARS-CoV-2 in vivo 
      and therefore do not support its application as a treatment against COVID-19 at a 
      dosage of 10 mg/kg/day.
CI  - Copyright (c) 2021 Elsevier Ltd and International Society of Antimicrobial 
      Chemotherapy. All rights reserved.
FAU - Muturi, Elishiba
AU  - Muturi E
AD  - CAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety 
      Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 
      430071, China; University of Chinese Academy of Sciences, Beijing 100049, China.
FAU - Hong, Wei
AU  - Hong W
AD  - CAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety 
      Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 
      430071, China; University of Chinese Academy of Sciences, Beijing 100049, China.
FAU - Li, Junhua
AU  - Li J
AD  - CAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety 
      Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 
      430071, China.
FAU - Yang, Wan
AU  - Yang W
AD  - State Key Laboratory of Agricultural Microbiology, College of Life Science and 
      Technology, Huazhong Agricultural University, Wuhan 430070, China.
FAU - He, Jin
AU  - He J
AD  - State Key Laboratory of Agricultural Microbiology, College of Life Science and 
      Technology, Huazhong Agricultural University, Wuhan 430070, China.
FAU - Wei, Hongping
AU  - Wei H
AD  - CAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety 
      Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 
      430071, China; University of Chinese Academy of Sciences, Beijing 100049, China. 
      Electronic address: hpwei@wh.iov.cn.
FAU - Yang, Hang
AU  - Yang H
AD  - CAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety 
      Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 
      430071, China; University of Chinese Academy of Sciences, Beijing 100049, China. 
      Electronic address: yangh@wh.iov.cn.
LA  - eng
PT  - Journal Article
DEP - 20211217
PL  - Netherlands
TA  - Int J Antimicrob Agents
JT  - International journal of antimicrobial agents
JID - 9111860
RN  - 0 (Antiviral Agents)
RN  - 0 (Protease Inhibitors)
RN  - 9WS5RD66HZ (Simeprevir)
RN  - EC 3.4.17.23 (ACE2 protein, human)
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
SB  - IM
MH  - Angiotensin-Converting Enzyme 2/*genetics
MH  - Animals
MH  - Antiviral Agents/*pharmacology/therapeutic use
MH  - COVID-19/virology
MH  - Chlorocebus aethiops
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Negative Results
MH  - Protease Inhibitors/*pharmacology/therapeutic use
MH  - SARS-CoV-2/*drug effects
MH  - Simeprevir/*pharmacology/therapeutic use
MH  - Vero Cells
MH  - Virus Replication/*drug effects
MH  - COVID-19 Drug Treatment
PMC - PMC8679493
OTO - NOTNLM
OT  - Antiviral efficacy
OT  - COVID-19
OT  - SARS-CoV-2
OT  - Simeprevir
COIS- Declaration of Competing Interest None declared.
EDAT- 2021/12/21 06:00
MHDA- 2022/01/21 06:00
PMCR- 2021/12/17
CRDT- 2021/12/20 20:15
PHST- 2021/10/05 00:00 [received]
PHST- 2021/12/02 00:00 [revised]
PHST- 2021/12/03 00:00 [accepted]
PHST- 2021/12/21 06:00 [pubmed]
PHST- 2022/01/21 06:00 [medline]
PHST- 2021/12/20 20:15 [entrez]
PHST- 2021/12/17 00:00 [pmc-release]
AID - S0924-8579(21)01340-6 [pii]
AID - 106499 [pii]
AID - 10.1016/j.ijantimicag.2021.106499 [doi]
PST - ppublish
SO  - Int J Antimicrob Agents. 2022 Jan;59(1):106499. doi: 
      10.1016/j.ijantimicag.2021.106499. Epub 2021 Dec 17.