Detalhes do Documento

Descrição

Made available in DSpace on 2021-06-25T11:46:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-15

Royal Society-Newton Advanced Fellowship

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Wellcome Trust

Chikungunya fever is a disease caused by the Chikungunya virus (CHIKV) that is transmitted by the bite of the female of Aedes sp. mosquito. The symptoms include fever, muscle aches, skin rash, and severe joint pains. The disease may develop into a chronic condition and joint pain for months or years. Currently, there is no effective antiviral treatment against CHIKV infection. Treatments based on natural compounds have been widely studied, as many drugs were produced by using natural molecules and their derivatives. Alpha-phellandrene (alpha-Phe) is a naturally occurring organic compound that is a ligand for ruthenium, forming the organometallic complex [Ru2Cl4(p-cymene)(2)] (RcP). Organometallic complexes have shown promising as candidate molecules to a new generation of compounds that presented relevant biological properties, however, there is a lack of knowledge concerning the anti-CHIKV activity of these complexes. The present work evaluated the effects of the RcP and its precursors, the hydrate ruthenium(III) chloride salt (RuCl3.xH(2)O) (Ru) and alpha-Phe, on CHIKV infection in vitro. To this, BHK-21 cells were infected with CHIKV-nanoluciferase (CHIKV-nanoluc), a viral construct harboring the nanoluciferase reporter gene, at the presence or absence of the compounds for 16 h. Cytotoxicity and impact on infectivity were analyzed. The results demonstrated that RcP exhibited a strong therapeutic potential judged by the selective index > 40. Antiviral effects of RcP on different stages of the CHIKV replicative cycle were investigated; the results showed that it affected early stages of virus infection reducing virus replication by 77% at non-cytotoxic concentrations. Further assays demonstrated the virucidal activity of the compound that completely blocked virus infectivity. In silico molecular docking calculations suggested different binding interactions between aromatic rings of RcP and the loop of amino acids of the E2 envelope CHIKV glycoprotein mainly through hydrophobic interactions. Additionally, infrared spectroscopy spectral analysis indicated interactions of RcP with CHIKV glycoproteins. These data suggest that RcP may act on CHIKV particles, disrupting virus entry to the host cells. Therefore, RcP may represent a strong candidate for the development of anti-CHIKV drugs.

Univ Fed Uberlandia, Inst Biomed Sci, Uberlandia, MG, Brazil

Sao Paulo State Univ, Inst Biosci Language & Exact Sci, Sao Jose Do Rio Preto, Brazil

Univ Fed Uberlandia, Inst Chem, Uberlandia, MG, Brazil

Univ Fed Uberlandia, Inst Biotechnol, Uberlandia, MG, Brazil

FACERES Med Sch, Sao Jose Do Rio Preto, Brazil

Univ Tartu, Inst Technol, Tartu, Estonia

Univ Leeds, Fac Biol Sci, Leeds, W Yorkshire, England

Univ Leeds, Astbury Ctr Struct Mol Biol, Leeds, W Yorkshire, England

Sao Paulo State Univ, Inst Biosci Language & Exact Sci, Sao Jose Do Rio Preto, Brazil

Royal Society-Newton Advanced Fellowship: NA 150195

CNPq: 445021/2014-4

CNPq: 304795/2018-6

FAPEMIG: APQ-00587-14/SICONV 793988/2013

FAPEMIG: CEX-APQ-02176-11

FAPEMIG: APQ-02872-16

FAPEMIG: APQ-03385-18

FAPESP: 2017/13341-1

CAPES: 001

CAPES: 88881.506794/2020-01

Wellcome Trust: 096670