The Mechanism of Action of L-Tyrosine Derivatives against Chikungunya Virus Infection In Vitro Depends on Structural Changes

被引:0
作者
Loaiza-Cano, Vanessa [1 ]
Hernandez-Mira, Estiven [1 ]
Pastrana-Restrepo, Manuel [2 ]
Galeano, Elkin [2 ]
Pardo-Rodriguez, Daniel [3 ]
Martinez-Gutierrez, Marlen [1 ,4 ]
机构
[1] Univ Cooperat Colombia, Fac Med Vet & Zootecnia, Grp Invest Ciencias Anim GRICA, Bucaramanga 680002, Colombia
[2] Univ Antioquia, Grp Invest Prod Nat Marinos, Medellin 050010, Colombia
[3] Univ Los Andes, Metabol Core Facil MetCore, Vice Presidency Res, Bogota 111711, Colombia
[4] Univ Antioquia, Escuela Microbiol, Grp Invest Microbiol Bas & Aplicada MICROBA, Medellin 050010, Colombia
关键词
antiviral; chikungunya virus; in vitro; tyrosine; computational biology; mechanism of action; ANTIVIRAL ACTIVITY; DENGUE VIRUS; REEMERGENCE; DOCKING;
D O I
10.3390/ijms25147972
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Although the disease caused by chikungunya virus (CHIKV) is of great interest to public health organizations around the world, there are still no authorized antivirals for its treatment. Previously, dihalogenated anti-CHIKV compounds derived from L-tyrosine (dH-Y) were identified as being effective against in vitro infection by this virus, so the objective of this study was to determine the mechanisms of its antiviral action. Six dH-Y compounds (C1 to C6) dihalogenated with bromine or chlorine and modified in their amino groups were evaluated by different in vitro antiviral strategies and in silico tools. When the cells were exposed before infection, all compounds decreased the expression of viral proteins; only C4, C5 and C6 inhibited the genome; and C1, C2 and C3 inhibited infectious viral particles (IVPs). Furthermore, C1 and C3 reduce adhesion, while C2 and C3 reduce internalization, which could be related to the in silico interaction with the fusion peptide of the E1 viral protein. Only C3, C4, C5 and C6 inhibited IVPs when the cells were exposed after infection, and their effect occurred in late stages after viral translation and replication, such as assembly, and not during budding. In summary, the structural changes of these compounds determine their mechanism of action. Additionally, C3 was the only compound that inhibited CHIKV infection at different stages of the replicative cycle, making it a compound of interest for conversion as a potential drug.
引用
收藏
页数:19
相关论文
共 64 条
  • [1] Canonical sampling through velocity rescaling
    Bussi, Giovanni
    Donadio, Davide
    Parrinello, Michele
    [J]. JOURNAL OF CHEMICAL PHYSICS, 2007, 126 (01)
  • [2] Broad Antiviral Activity of Ginkgolic Acid against Chikungunya, Mayaro, Una, and Zika Viruses
    Campos, Dalkiria
    Navarro, Susana
    Yadira Llamas-Gonzalez, Yessica
    Sugasti, Madelaine
    Gonzalez-Santamaria, Jose
    [J]. VIRUSES-BASEL, 2020, 12 (04):
  • [3] MORPHOLOGICAL DEVELOPMENT OF CHIKUNGUNYA VIRUS
    CHAIN, MMT
    DOANE, FW
    MCLEAN, DM
    [J]. CANADIAN JOURNAL OF MICROBIOLOGY, 1966, 12 (05) : 895 - +
  • [4] Analysis of HIV wild-type and mutant structures via in silico docking against diverse ligand libraries
    Chang, Max W.
    Lindstrom, William
    Olson, Arthur J.
    Belew, Richard K.
    [J]. JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2007, 47 (03) : 1258 - 1262
  • [5] The role of enhanced aromatic π-electron donating aptitude of the tyrosyl sidechain with respect to that of phenylalanyl in intramolecular interactions
    Chass, GA
    Lovas, S
    Murphy, RF
    Csizmadia, IG
    [J]. EUROPEAN PHYSICAL JOURNAL D, 2002, 20 (03) : 481 - 497
  • [6] SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules
    Daina, Antoine
    Michielin, Olivier
    Zoete, Vincent
    [J]. SCIENTIFIC REPORTS, 2017, 7
  • [7] Aedes aegypti control strategies: a review
    de Sene Amancio Zara, Ana Laura
    dos Santos, Sandra Maria
    Fernandes-Oliveira, Ellen Synthia
    Carvalho, Roberta Gomes
    Coelho, Giovanini Evelim
    [J]. EPIDEMIOLOGIA E SERVICOS DE SAUDE, 2016, 25 (02): : 391 - 404
  • [8] Pathophysiology of chikungunya virus infection associated with fatal outcomes
    de Souza, William M.
    Fumagalli, Marcilio J.
    de Lima, Shirlene T. S.
    Parise, Pierina L.
    Carvalho, Deyse C. M.
    Hernandez, Cristian
    de Jesus, Ronaldo
    Delafiori, Jeany
    Candido, Darlan S.
    Carregari, Victor C.
    Muraro, Stefanie P.
    Souza, Gabriela F.
    Mello, Leda M. Simoes
    Claro, Ingra M.
    Diaz, Yamilka
    Kato, Rodrigo B.
    Trentin, Lucas N.
    Costa, Clauber H. S.
    Maximo, Ana Carolina B. M.
    Cavalcante, Karene F.
    Fiuza, Tayna S.
    Viana, Vania A. F.
    Melo, Maria Elisabeth L.
    Ferraz, Clarissa P. M.
    Silva, Debora B.
    Duarte, Larissa M. F.
    Barbosa, Priscilla P.
    Amorim, Mariene R.
    Judice, Carla C.
    Toledo-Teixeira, Daniel A.
    Ramundo, Mariana S.
    Aguilar, Patricia, V
    Araujo, Emerson L. L.
    Costa, Fabio T. M.
    Cerqueira-Silva, Thiago
    Khouri, Ricardo
    Boaventura, Viviane S.
    Figueiredo, Luiz Tadeu M.
    Fang, Rong
    Moreno, Brechla
    Lopez-Verges, Sandra
    Mello, Liana Perdigao
    Skaf, Munir S.
    Catharino, Rodrigo R.
    Granja, Fabiana
    Martins-de-Souza, Daniel
    Plante, Jessica A.
    Plante, Kenneth S.
    Sabino, Ester C.
    Diamond, Michael S.
    [J]. CELL HOST & MICROBE, 2024, 32 (04) : 606 - 622.e8
  • [9] El Sayed K.A., 2000, Stud. Nat. Prod. Chem., V24, P473, DOI DOI 10.1016/S1572-5995(00)80051-4
  • [10] Interleukin 27 as an inducer of antiviral response against chikungunya virus infection in human macrophages
    Felipe Valdes-Lopez, Juan
    Fernandez, Geysson J.
    Urcuqui-Inchima, Silvio
    [J]. CELLULAR IMMUNOLOGY, 2021, 367