Natasha Cristina da Rocha, Leonardo dos Santos Corrêa Amorim, Vitor Won-Held Rabelo, Carolina Oliveira da Silva, Luciene Soares Silva, Geicy Kelly Pires Barboza, Mariana Falcão Lopes Princisval Carlos, Aurea Echevarria Aznar Neves Lima, Izabel Christina Nunes de Palmer Paixão
{"title":"β-enaminoester derivatives exhibit promising in vitro and in silico antiviral potential against Mayaro virus","authors":"Natasha Cristina da Rocha, Leonardo dos Santos Corrêa Amorim, Vitor Won-Held Rabelo, Carolina Oliveira da Silva, Luciene Soares Silva, Geicy Kelly Pires Barboza, Mariana Falcão Lopes Princisval Carlos, Aurea Echevarria Aznar Neves Lima, Izabel Christina Nunes de Palmer Paixão","doi":"10.1007/s00203-024-04135-9","DOIUrl":null,"url":null,"abstract":"<div><p>Mayaro virus (MAYV) is the causative agent of Mayaro fever, which is characterized mainly by acute fever and long-term severe arthralgia, common manifestations of other arbovirus infections, making the correct diagnosis a challenge. Besides, MAYV infections have been reported in South America, especially in Brazil. However, the lack of vaccines or specific antiviral drugs to control these infections makes the search for new antivirals an urgent need. Herein, we evaluated the antiviral potential of synthetic β-enaminoesters derivatives against MAYV replication and their pharmacokinetic and toxicological (ADMET) properties using in vitro and in silico strategies. For this purpose, Vero cells were infected with MAYV at an MOI of 0.1, treated with compounds (50 µM) for 24 h, and virus titers were quantified by plaque reduction assays. Compounds <b>2b</b> (83.33%) and <b>2d</b> (77.53%) exhibited the highest activity with inhibition rates of 83.33% and 77.53%, respectively. The most active compounds <b>2b</b> (EC<sub>50</sub> = 18.92 µM; SI > 52.85), and <b>2d</b> (EC<sub>50</sub> = 14.52 µM; SI > 68.87) exhibited higher potency and selectivity than the control drug suramin (EC<sub>50</sub> = 38.97 µM; SI > 25.66). Then, we investigated the mechanism of action of the most active compounds. None of the compounds showed virucidal activity, neither inhibited virus adsorption, but compound <b>2b</b> inhibited virus entry (62.64%). Also, compounds <b>2b</b> and <b>2d</b> inhibited some processes involved with the release of new virus particles. Finally, in silico results indicated good ADMET parameters of the most active compounds and reinforced their promising profile as drug candidates against MAYV.</p></div>","PeriodicalId":8279,"journal":{"name":"Archives of Microbiology","volume":"206 10","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Microbiology","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s00203-024-04135-9","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Mayaro virus (MAYV) is the causative agent of Mayaro fever, which is characterized mainly by acute fever and long-term severe arthralgia, common manifestations of other arbovirus infections, making the correct diagnosis a challenge. Besides, MAYV infections have been reported in South America, especially in Brazil. However, the lack of vaccines or specific antiviral drugs to control these infections makes the search for new antivirals an urgent need. Herein, we evaluated the antiviral potential of synthetic β-enaminoesters derivatives against MAYV replication and their pharmacokinetic and toxicological (ADMET) properties using in vitro and in silico strategies. For this purpose, Vero cells were infected with MAYV at an MOI of 0.1, treated with compounds (50 µM) for 24 h, and virus titers were quantified by plaque reduction assays. Compounds 2b (83.33%) and 2d (77.53%) exhibited the highest activity with inhibition rates of 83.33% and 77.53%, respectively. The most active compounds 2b (EC50 = 18.92 µM; SI > 52.85), and 2d (EC50 = 14.52 µM; SI > 68.87) exhibited higher potency and selectivity than the control drug suramin (EC50 = 38.97 µM; SI > 25.66). Then, we investigated the mechanism of action of the most active compounds. None of the compounds showed virucidal activity, neither inhibited virus adsorption, but compound 2b inhibited virus entry (62.64%). Also, compounds 2b and 2d inhibited some processes involved with the release of new virus particles. Finally, in silico results indicated good ADMET parameters of the most active compounds and reinforced their promising profile as drug candidates against MAYV.
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