Antiviral evaluation of 1,4-disubstituted-1,2,3-triazole derivatives against Chikungunya virus

Author:

Rabelo Vitor Won-Held1ORCID,da Silva Verônica Diniz2,Sanchez Nuñez Maria Leonisa1ORCID,Santos Corrêa Amorim Leonardo dos13ORCID,Buarque Camilla Djenne2ORCID,Kuhn Richard J45ORCID,Abreu Paula Alvarez6ORCID,Nunes de Palmer Paixão Izabel Christina178ORCID

Affiliation:

1. Programa de Pós-graduação em Ciências e Biotecnologia, Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, CEP, 24210-201, Brazil

2. Laboratório de Síntese Orgânica, Pontifícia Universidade Católica do Rio de Janeiro, Rio de Janeiro, RJ, CEP, 22451-900, Brazil

3. Gerência de Desenvolvimento Tecnológico, Instituto Vital Brazil, Niterói, RJ, 24230-410, Brazil

4. Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA

5. Purdue Institute of Inflammation, Immunology, & Infectious Disease, Purdue University, West Lafayette, IN 47907, USA

6. Instituto de Biodiversidade e Sustentabilidade (NUPEM), Universidade Federal do Rio de Janeiro, Macaé, RJ, CEP, 27965-045, Brazil

7. Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, CEP, 24210-201, Brazil

8. Programas de Pós-graduação em Biotecnologia Marinha e de Neurologia, Universidade Federal Fluminense, Niterói, RJ, Brazil

Abstract

Aim: This work aimed to investigate the antiviral activity of two 1,4-disubstituted-1,2,3-triazole derivatives (1 and 2) against Chikungunya virus (CHIKV) replication. Materials & methods: Cytotoxicity was analyzed using colorimetric assays and the antiviral potential was evaluated using plaque assays and computational tools. Results: Compound 2 showed antiviral activity against CHIKV 181-25 in BHK-21 and Vero cells. Also, this compound presented a higher activity against CHIKV BRA/RJ/18 in Vero cells, like compound 1. Compound 2 exhibited virucidal activity and inhibited virus entry while compound 1 inhibited virus release. Molecular docking suggested that these derivatives inhibit nsP1 protein while compound 1 may also target capsid protein. Conclusion: Both compounds exhibit promising antiviral activity against CHIKV by blocking different steps of virus replication.

Funder

National Institute of Allergy and Infectious Diseases

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro

Publisher

Future Medicine Ltd

Subject

Virology

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