Memantine hydrochloride: a drug to be repurposed against Chikungunya virus?

Autor(es)

dos Santos Pereira, Anna Karla ^[1] ; Santos, Igor A. ^[2] ; da Silva, Washington W. ^[3] ; Resende Nogueira, Flavia A. ^[3] ; Bergamini, Fernando R. G. ^[4] ; Jardim, Ana Carolina G. ^[2] ; Corbi, Pedro P. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Inst Chem, BR-13083871 Campinas, SP - Brazil

^[2] Univ Fed Uberlandia, Inst Biomed Sci, Lab Virol, BR-38405302 Uberlandia, MG - Brazil

^[3] Univ Araraquara UNIARA, Dept Biol & Hlth Sci, Araraquara, SP - Brazil

^[4] Univ Fed Uberlandia, Inst Chem, Lab Synth Bioinspired Mol, BR-34000902 Uberlandia, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PHARMACOLOGICAL REPORTS; v. 73, n. 3 FEB 2021.
• Citações Web of Science: 1

Resumo

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 mu M. The effective concentration of 50% inhibition (EC50) was calculated. Cell viability assay (determination of CC50) was also performed employing BHK-21 cells. Mutagenic assays were performed by the Salmonella Typhimurium/microsome assay (Ames test). Results MtnH presented a CC50 of 248.4 +/- 31.9 mu M and an EC50 of 32.4 +/- 4 mu M 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. {[}GRAPHICS] . (AU)

• Processo FAPESP: 18/12062-4 - Síntese, caracterização e estudos de interação com biomoléculas de complexos metálicos contendo ligantes biologicamente ativos: uma estratégia na preparação de novos agentes com atividades antibacterianas e antivirais
• Beneficiário: Pedro Paulo Corbi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/16278-9 - Estudo do potencial genotoxicológico e da permeabilidade em células Caco-2 de complexos metálicos com promissoras atividades biológicas
• Beneficiário: Flávia Aparecida Resende Nogueira
• Modalidade de apoio: Auxílio à Pesquisa - Regular