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合成化合物对马亚罗病毒抗病毒活性的鉴定与表征

Identification and Characterization of Antiviral Activity of Synthetic Compounds Against Mayaro Virus.

作者信息

Andreolla Ana Paula, Koishi Andrea Cristine, Borges Alessandra Abel, Oliveira Larissa Albuquerque de, Oliveira Viviane Guedes de, Lima Nerilson Marques, Ávila Eloah Pereira, de Castro Pedro Pôssa, Amarante Giovanni Wilson, de Almeida Mauro Vieira, Bordignon Juliano, Duarte Dos Santos Claudia Nunes

机构信息

Laboratório de Virologia Molecular, Instituto Carlos Chagas, ICC/Fiocruz, Rua Prof. Algacyr Munhoz Mader 3775, Cidade Industrial de Curitiba, Curitiba 81350-010, Paraná, Brazil.

Laboratório de Pesquisas em Virologia e Imunologia, Instituto de Ciências Biológicas e da Saúde (ICBS), Universidade Federal de Alagoas (UFAL), Av. Lourival Melo Mota, s/n, Tabuleiro do Martins, Maceió 57072-900, Alagoas, Brazil.

出版信息

Pharmaceuticals (Basel). 2025 May 13;18(5):717. doi: 10.3390/ph18050717.

DOI:10.3390/ph18050717
PMID:40430536
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12115251/
Abstract

In Brazil, the co-circulation of arboviruses-such as dengue, Zika, yellow fever, and Chikungunya viruses-creates a complex epidemiological landscape, drawing attention from health authorities due to high morbidity and mortality rates. Also present in this context is the Mayaro virus (MAYV), a neglected arbovirus, which can also cause severe syndromes and has been expanding beyond its usual endemic areas in northern and central-western Brazil. Epidemiological surveillance measures remain limited, and there are no effective prophylactic strategies or antiviral treatments for this neglected arbovirus. In this study, we evaluated the antiviral activity of commercial and synthetic compounds against MAYV using an image high-throughput screening (iHTS) system. A total of 52 compounds from an FDA-approved commercial library (Tocriscreen) and 50 other compounds were tested. Seven compounds showed anti-MAYV activity and were non-toxic for the following cell lines: Naringenin, LLA9A, chrysin, and its ester C6. Post-infection treatments with these selected compounds significantly decreased the percentage of infected cells and the release of infectious viral particles in the supernatant. Additionally, anti-MAYV activity of these four selected hits was confirmed using several human cell lines and two different MAYV genotypes. Our results indicate that the iHTS platform is effective for screening anti-MAYV drugs and that four promising compounds can efficiently inhibit MAYV replication in human cell lines. Although in vivo studies are still required to confirm the efficacy of the selected hits, our findings provide a starting point for developing a potential treatment for MAYV infections.

摘要

在巴西,登革热、寨卡、黄热病和基孔肯雅病毒等虫媒病毒共同传播,形成了复杂的流行病学态势,因其高发病率和死亡率而引起了卫生当局的关注。同样存在于这种背景下的还有马亚罗病毒(MAYV),一种被忽视的虫媒病毒,它也可导致严重综合征,并且已在巴西北部和中西部其通常的流行区域之外不断扩散。流行病学监测措施仍然有限,对于这种被忽视的虫媒病毒,尚无有效的预防策略或抗病毒治疗方法。在本研究中,我们使用图像高通量筛选(iHTS)系统评估了商业化合物和合成化合物对MAYV的抗病毒活性。对来自FDA批准的商业文库(Tocriscreen)的52种化合物以及其他50种化合物进行了测试。七种化合物显示出抗MAYV活性,并且对以下细胞系无毒:柚皮素、LLA9A、白杨素及其酯C6。用这些选定的化合物进行感染后处理,可显著降低感染细胞的百分比以及上清液中传染性病毒颗粒的释放。此外,使用几种人类细胞系和两种不同的MAYV基因型证实了这四种选定化合物的抗MAYV活性。我们的结果表明,iHTS平台对于筛选抗MAYV药物是有效的,并且四种有前景的化合物可以有效抑制MAYV在人类细胞系中的复制。尽管仍需要进行体内研究来确认选定化合物的疗效,但我们的发现为开发针对MAYV感染的潜在治疗方法提供了一个起点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/72daaa8dbcb0/pharmaceuticals-18-00717-sch003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/dea3f616dfba/pharmaceuticals-18-00717-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/61b5a2942228/pharmaceuticals-18-00717-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/25da64460426/pharmaceuticals-18-00717-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/77f5401d253d/pharmaceuticals-18-00717-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/d646c0189434/pharmaceuticals-18-00717-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/e491eda610c7/pharmaceuticals-18-00717-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/43a8edbe7f86/pharmaceuticals-18-00717-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/36a30e55127c/pharmaceuticals-18-00717-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/72daaa8dbcb0/pharmaceuticals-18-00717-sch003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/dea3f616dfba/pharmaceuticals-18-00717-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/61b5a2942228/pharmaceuticals-18-00717-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/25da64460426/pharmaceuticals-18-00717-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/77f5401d253d/pharmaceuticals-18-00717-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/d646c0189434/pharmaceuticals-18-00717-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/e491eda610c7/pharmaceuticals-18-00717-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/43a8edbe7f86/pharmaceuticals-18-00717-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/36a30e55127c/pharmaceuticals-18-00717-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f00/12115251/72daaa8dbcb0/pharmaceuticals-18-00717-sch003.jpg

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本文引用的文献

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Potential antiviral activities of chrysin against hepatitis B virus.
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Mayaro Virus: The State-of-the-Art for Antiviral Drug Development.马亚罗病毒:抗病毒药物研发的最新进展。
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Targeting Host PIM Protein Kinases Reduces Mayaro Virus Replication.靶向宿主 PIM 蛋白激酶可降低马亚罗病毒的复制。
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