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Targeting Chikungunya Virus Entry: Alternatives for New Inhibitors in Drug Discovery

Author(s):

Leandro Rocha Silva, Érica Erlanny da Silva Rodrigues, Jamile Taniele-Silva, Letícia Anderson, João Xavier de Araújo-Júnior, Ênio José Bassi and Edeildo F. da Silva-Júnior*   Pages 1 - 23 ( 23 )

Abstract:


Chikungunya virus (CHIKV) is an Alphavirus (Togaviridae) responsible for Chikungunya fever (CHIKF) that is mainly characterized by a severe polyarthralgia, in which it is transmitted by the bite of infected Aedes aegypti and Ae. albopictus mosquitoes. Nowadays, there are no licensed vaccines or approved drugs to specifically treat this viral disease. Structural viral proteins participate in key steps of its replication cycle, such as viral entry, membrane fusion, nucleocapsid assembly, and virus budding. In this context, envelope E3-E2-E1 glycoproteins complex could be targeted for designing new drug candidates. In this review, aspects of the CHIKV entry mechanism are discussed to provide insights into assisting the drug discovery process. Moreover, several naturals, naturebased and synthetic compounds, as well as repurposed drugs and virtual screening are also explored as alternatives for developing CHIKV entry inhibitors. Finally, we provided a complementary analysis of studies involving inhibitors that were not explored by in silico methods. Based on this, Phe118, Val179, and Lys181 were found to be the most frequent residues, being present in 89.6, 82.7, and 93.1% of complexes, respectively. Lastly, some chemical aspects associated with interactions of these inhibitors and mature envelope E3- E2-E1 glycoproteins’ complex were discussed to provide data for scientists worldwide, supporting their search for new inhibitors against this emerging arbovirus.

Keywords:

Entry inhibitors, Chikungunya virus, medicinal chemistry, drug design, repurposing, natural products, synthetic, virtual screening, molecular docking, frequency residues.

Affiliation:

Chemistry and Biotechnology Institute, Federal University of Alagoas, Campus A.C. Simões, Lourival Melo Mota Avenue, Maceió 57072-970, Chemistry and Biotechnology Institute, Federal University of Alagoas, Campus A.C. Simões, Lourival Melo Mota Avenue, Maceió 57072-970, IMUNOREG – Immunoregulation Research Group, Laboratory of Research in Virology and Immunology, Institute of Biological Sciences and Health, Federal University of Alagoas, Campus AC. Simões, Lourival Melo Mota Avenue, Maceió 57072-970, IMUNOREG – Immunoregulation Research Group, Laboratory of Research in Virology and Immunology, Institute of Biological Sciences and Health, Federal University of Alagoas, Campus AC. Simões, Lourival Melo Mota Avenue, Maceió 57072-970, Chemistry and Biotechnology Institute, Federal University of Alagoas, Campus A.C. Simões, Lourival Melo Mota Avenue, Maceió 57072-970, IMUNOREG – Immunoregulation Research Group, Laboratory of Research in Virology and Immunology, Institute of Biological Sciences and Health, Federal University of Alagoas, Campus AC. Simões, Lourival Melo Mota Avenue, Maceió 57072-970, Chemistry and Biotechnology Institute, Federal University of Alagoas, Campus A.C. Simões, Lourival Melo Mota Avenue, Maceió 57072-970



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