PMID- 33523405
OWN - NLM
STAT- MEDLINE
DCOM- 20211207
LR  - 20211214
IS  - 2299-5684 (Electronic)
IS  - 1734-1140 (Print)
IS  - 1734-1140 (Linking)
VI  - 73
IP  - 3
DP  - 2021 Jun
TI  - Memantine hydrochloride: a drug to be repurposed against Chikungunya virus?
PG  - 954-961
LID - 10.1007/s43440-021-00216-4 [doi]
AB  - BACKGROUND: Chikungunya fever is an endemic disease caused by the Chikungunya 
      virus (CHIKV) to which there is no vaccine or effective antiviral drug treatment 
      so far. Our study aimed to evaluate the potential anti-CHIKV activity of 
      memantine hydrochloride (mtnH), a drug from the class of the aminoadamantanes 
      approved for the treatment of Alzheimer s disease, as a possible drug to be 
      repurposed to the treatment of Chikungunya fever. METHODS: MtnH antiviral 
      activity against CHIKV was determined by infecting BHK-21 cells with 
      CHIKV-nanoluc, a virus carrying the marker nanoluciferase reporter, in the 
      presence or absence of mtnH at concentrations ranging from 500 to 1.45 microM. The 
      effective concentration of 50% inhibition (EC(50)) was calculated. Cell viability 
      assay (determination of CC(50)) was also performed employing BHK-21 cells. 
      Mutagenic assays were performed by the Salmonella Typhimurium/microsome assay 
      (Ames test). RESULTS: MtnH presented a CC(50) of 248.4 +/- 31.9 microM and an EC(50) of 
      32.4 +/- 4 microM against CHIKV in vitro. The calculated selectivity index (SI) was 
      7.67. MtnH did not induce genetic mutation in Salmonella strains with or without 
      an external metabolizing system. CONCLUSION: With the data herein presented, it 
      is possible to hypothesize mtnH as a viable candidate to be repurposed as an 
      anti-CHIKV drug. Clinical assays are, therefore, encouraged due to the promising 
      in vitro results. The drug memantine hydrochloride is herein personified with a 
      doubt: as a prior regulated drug against Alzheimer, could it follow the path 
      against Chikungunya virus too?
FAU - Pereira, Anna Karla Dos Santos
AU  - Pereira AKDS
AD  - Institute of Chemistry, University of Campinas-UNICAMP, Campinas, SP, 13083-871, 
      Brazil.
FAU - Santos, Igor A
AU  - Santos IA
AD  - Laboratory of Virology, Institute of Biomedical Sciences, Federal University of 
      Uberlandia, Uberlandia, MG, 38405-302, Brazil.
FAU - da Silva, Washington W
AU  - da Silva WW
AD  - Department of Biological and Health Sciences, University of Araraquara-UNIARA, 
      Araraquara, SP, Brazil.
FAU - Nogueira, Flavia A Resende
AU  - Nogueira FAR
AD  - Department of Biological and Health Sciences, University of Araraquara-UNIARA, 
      Araraquara, SP, Brazil.
FAU - Bergamini, Fernando R G
AU  - Bergamini FRG
AUID- ORCID: 0000-0002-8357-3044
AD  - Laboratory of Synthesis of Bioinspired Molecules, Institute of Chemistry, Federal 
      University of Uberlandia, Uberlandia, MG, 34000-902, Brazil. bergamini@ufu.br.
FAU - Jardim, Ana Carolina G
AU  - Jardim ACG
AUID- ORCID: 0000-0002-6348-7923
AD  - Laboratory of Virology, Institute of Biomedical Sciences, Federal University of 
      Uberlandia, Uberlandia, MG, 38405-302, Brazil. jardim@ufu.br.
FAU - Corbi, Pedro P
AU  - Corbi PP
AUID- ORCID: 0000-0002-7478-0877
AD  - Institute of Chemistry, University of Campinas-UNICAMP, Campinas, SP, 13083-871, 
      Brazil. ppcorbi@unicamp.br.
LA  - eng
PT  - Journal Article
DEP - 20210201
PL  - Switzerland
TA  - Pharmacol Rep
JT  - Pharmacological reports : PR
JID - 101234999
RN  - 0 (Antiviral Agents)
RN  - W8O17SJF3T (Memantine)
SB  - IM
MH  - Antiviral Agents/*pharmacology
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Chikungunya Fever/*drug therapy/virology
MH  - Chikungunya virus/*drug effects
MH  - Humans
MH  - Memantine/*pharmacology
PMC - PMC7848042
OTO - NOTNLM
OT  - Antiviral
OT  - Chikungunya virus
OT  - Drug
OT  - Memantine hydrochloride
OT  - Repurposing
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/02/02 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/02/01
CRDT- 2021/02/01 12:22
PHST- 2020/10/14 00:00 [received]
PHST- 2021/01/05 00:00 [accepted]
PHST- 2020/12/30 00:00 [revised]
PHST- 2021/02/02 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/02/01 12:22 [entrez]
PHST- 2021/02/01 00:00 [pmc-release]
AID - 10.1007/s43440-021-00216-4 [pii]
AID - 216 [pii]
AID - 10.1007/s43440-021-00216-4 [doi]
PST - ppublish
SO  - Pharmacol Rep. 2021 Jun;73(3):954-961. doi: 10.1007/s43440-021-00216-4. Epub 2021 
      Feb 1.