化学
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)
2019年冠状病毒病(COVID-19)
石蒜科
2019-20冠状病毒爆发
石蒜科生物碱
病毒学
配体(生物化学)
计算生物学
立体化学
生物碱
生物化学
植物
受体
生物
传染病(医学专业)
医学
疾病
病理
爆发
作者
Deborah Kimie Yonamine,Vitor Eduardo Narciso dos Reis,Amanda Eiriz Feu,Warley de Souza Borges,Carmen L. Cardoso,Taísa Magnani Dinamarco
标识
DOI:10.1016/j.jpba.2023.115935
摘要
Ligand fishing, also described as affinity-based assay, represents a convenient and efficient approach to separate potential ligands from complex matrixes or chemical libraries. This approach contributes to the identification of lead compounds that can bind to a specific target. In the context of COVID-19, the search for novel therapeutic agents is crucial. Small molecule-based antiviral drugs, such as Amaryllidaceae alkaloids, have been described as potential candidates because they can inhibit RNA viruses. Among various SARS-CoV-2 proteins, Nsp3, Nsp4, and Nsp6 play a crucial role in the pathogenicity of the virus and are attractive targets for developing COVID-19 treatments. These proteins are responsible for the replication/transcription complex (RTC) within double-membrane vesicles (DMVs), and their inhibition disrupts the virus's infectious cycle. Herein, we have successfully expressed and immobilized the SARS-CoV-2 Nsp4 protein on magnetic beads (Nsp4-MBs) and employed a ligand fishing assay to screen a collection of ten Amaryllidaceae-based alkaloids and applied to Hippeastrum aulicum extract. Remarkably, four out of ten alkaloids, namely 2-α-7-dimethoxyhomolycorine (6), haemanthamine (5), albomaculine (8), and tazettine (9), exhibited selective affinities for Nsp4. Albomaculine (8) and haemanthamine (5) were also identified from extract by the affinity assay. These findings highlight the potential of these alkaloids as model compounds for future drug discovery studies aimed at developing therapeutic interventions against SARS-CoV-2 infections.
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