Brefeldin A and Cytochalasin B reduce dengue virus replication in cell cultures but do not protect mice against viral challenge

Kleber Juvenal Silva Farias; Paula Renata Lima Machado; Renato Ferreira de Almeida Júnior; Benedito Antônio Lopes da Fonseca

doi:10.1099/acmi.0.000041

Brefeldin A and Cytochalasin B reduce dengue virus replication in cell cultures but do not protect mice against viral challenge

Access Microbiol. 2019 Jul 22;1(6):e000041. doi: 10.1099/acmi.0.000041. eCollection 2019.

Authors

Kleber Juvenal Silva Farias^{1

2}, Paula Renata Lima Machado³, Renato Ferreira de Almeida Júnior³, Benedito Antônio Lopes da Fonseca¹

Affiliations

¹ Department of Internal Medicine, School of Medicine of Ribeirao Preto - University of Sao Paulo, Avenida Bandeirantes, 3900, Monte Alegre, 14049-900, Ribeirao Preto SP, Brazil.
² Program of Graduate Studies on Applied Microbiology and Immunology, School of Medicine of Ribeirao Preto - University of Sao Paulo, Avenida Bandeirantes, 3900, Monte Alegre, 14049-900, Ribeirão Preto SP, Brazil.
³ Department of Clinical Analysis and Toxicology, Federal University of Rio Grande do Norte, Street General Gustavo Cordeiro de Farias, 384, Petropolis, 59012-570 Natal, RN, Brazil.

Abstract

Background: Dengue is an emerging arboviral disease caused by dengue virus (DENV). DENV belongs to the family Flaviviridae and genus Flavivirus. No specific anti-DENV drugs are currently available.

Methods: We investigated the antiviral activity of Brefeldin A (BFA) and Cytochalasin B (CB) against this infection. The drugs BFA and CB were used in the in vitro treatment of dengue-2 virus (DENV-2) infections in Vero cell cultures and in protection from lethality by post-challenge administration in Swiss mice. Viral load was quantified by qRT-PCR and plaque assay in Vero cell cultures, post-infection, treated or not with the drugs. Post-challenge drug levels were evaluated by survival analysis.

Results: Our results indicate that doses of 5 µg ml^-1 of BFA and 10 µg ml^-1 of CB are not toxic to the cells and induce a statistically significant inhibition of DENV-2 replication in Vero cells when compared to control. No BFA- or CB-treated mice survived the challenge with DENV-2.

Conclusion: These data suggest that BFA and CB have an antiviral action against DENV-2 replication in Vero cell culture, but do not alter infected mice mortality.

Keywords: BFA; CB; Cell Culture; DENV-2; Mice; Viral load monitoring; qRT-PCR.