Antiviral activity of ouabain against a Brazilian Zika virus strain.

Autor:	Carvalho DCM; Laboratory of Immunobiotechnology, Biotechnology Center, Federal University of Paraiba (UFPB), João Pessoa, Paraiba, Brazil.; Department of Virology and Experimental Therapy, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Pernambuco, Brazil., da Silva PG; Department of Virology and Experimental Therapy, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Pernambuco, Brazil., Dantas WM; Department of Virology and Experimental Therapy, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Pernambuco, Brazil.; Department of Chemistry, Federal Rural University of Pernambuco (UFRPE), Recife, Pernambuco, Brazil., da Silva SJR; Department of Virology and Experimental Therapy, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Pernambuco, Brazil., da Silva CTA; Department of Virology and Experimental Therapy, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Pernambuco, Brazil., Chaves EJF; Laboratory of Molecular and Cellular Biotechnology, Department of Biotechnology, Federal University of Paraiba (UFPB), João Pessoa, Paraiba, Brazil., de Araújo DAM; Laboratory of Molecular and Cellular Biotechnology, Department of Biotechnology, Federal University of Paraiba (UFPB), João Pessoa, Paraiba, Brazil., de Oliveira RN; Department of Chemistry, Federal Rural University of Pernambuco (UFRPE), Recife, Pernambuco, Brazil., Rodrigues-Mascarenhas S; Laboratory of Immunobiotechnology, Biotechnology Center, Federal University of Paraiba (UFPB), João Pessoa, Paraiba, Brazil. sandra@cbiotec.ufpb.br., Pena LJ; Department of Virology and Experimental Therapy, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (Fiocruz), Recife, Pernambuco, Brazil. lindomar.pena@fiocruz.br.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2022 Jul 23; Vol. 12 (1), pp. 12598. Date of Electronic Publication: 2022 Jul 23.
DOI:	10.1038/s41598-022-14243-5
Abstrakt:	Zika virus (ZIKV) is an emerging arbovirus associated with neurological disorders. Currently, no specific vaccines or antivirals are available to treat the ZIKV infection. Ouabain, a cardiotonic steroid known as Na + /K + -ATPase inhibitor, has been previously described as an immunomodulatory substance by our group. Here, we evaluated for the first time the antiviral activity of this promising substance against a Brazilian ZIKV strain. Vero cells were treated with different concentrations of ouabain before and after the infection with ZIKV. The antiviral effect was evaluated by the TCID 50 method and RT-qPCR. Ouabain presented a dose-dependent inhibitory effect against ZIKV, mainly when added post infection. The reduction of infectious virus was accompanied by a decrease in ZIKV RNA levels, suggesting that the mechanism of ZIKV inhibition by ouabain occurred at the replication step. In addition, our in silico data demonstrated a conformational stability and favorable binding free energy of ouabain in the biding sites of the NS5-RdRp and NS3-helicase proteins, which could be related to its mechanism of action. Taken together, these data demonstrate the antiviral activity of ouabain against a Brazilian ZIKV strain and evidence the potential of cardiotonic steroids as promising antiviral agents. (© 2022. The Author(s).)
Databáze:	MEDLINE
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