Bamrung Phonphiphat, Toviwek Borvornwat, Samsudin Firdaus, Chairatana Phoom, Bond Peter John, Pongprayoon Prapasiri
Department of Chemistry, Faculty of Science, Kasetsart University, Chatuchak, Bangkok 10900, Thailand.
Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), 30 Biopolis Street, #07-01 Matrix, Singapore 138671, Singapore.
Int J Mol Sci. 2025 Apr 25;26(9):4100. doi: 10.3390/ijms26094100.
The emergence of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a global issue since 2019. The prominent characteristic of SARS-CoV-2 is the presence of the spike (S) protein protruding from the virus particle envelope. The S protein is a major drug and vaccine target because it initiates the key step in infection. Medicinal herbs are a potential treatment option to enhance immunity to fight viral infections. L. has been reported to display promising anti-viral activities. Specifically, brazilin (BRA), a major bioactive compound in , was reported to play a role in inhibiting viral infection. Thus, the ability of BRA as a COVID-19 treatment was tested. The S protein was used as the BRA target of this work. Understanding the binding mechanism of BRA to the S protein is crucial for future utilisation of as a COVID-19 treatment or other coronavirus-caused pandemics. Here, we performed molecular docking of BRA onto the S protein receptor binding domain (RBD) and multimerisation (MM) pockets. Molecular dynamics (MD) simulations were conducted to study the stability of binding to glycosylated and non-glycosylated S protein constructs. BRA can bind to the Receptor-binding motif (RBM) on an RBD surface stably; however, it is too large to fit into the MM pocket, resulting in dissociation. Nonetheless, BRA is bound by residues near the S1/S2 interface. We found that glycosylation has no effect on BRA binding, as the proposed binding site is far from any glycans. Our results thus indicate that may act as a promising preventive and therapeutic alternative for COVID-19 treatment.
自2019年以来，由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的冠状病毒病（COVID-19）已成为一个全球性问题。SARS-CoV-2的突出特征是病毒颗粒包膜上存在刺突（S）蛋白。S蛋白是主要的药物和疫苗靶点，因为它启动了感染的关键步骤。草药是增强免疫力以对抗病毒感染的一种潜在治疗选择。已有报道称[植物名称未给出]具有有前景的抗病毒活性。具体而言，[植物名称未给出]中的主要生物活性化合物巴西苏木素（BRA）据报道在抑制病毒感染中发挥作用。因此，测试了BRA作为COVID-19治疗药物的能力。S蛋白被用作这项工作中BRA的靶点。了解BRA与S蛋白的结合机制对于未来将[植物名称未给出]用作COVID-19治疗或其他冠状病毒引起的大流行至关重要。在此，我们对BRA与S蛋白受体结合域（RBD）和多聚化（MM）口袋进行了分子对接。进行了分子动力学（MD）模拟以研究与糖基化和非糖基化S蛋白构建体结合的稳定性。BRA可以稳定地结合到RBD表面的受体结合基序（RBM）上；然而，它太大而无法进入MM口袋，导致解离。尽管如此，BRA被S1/S2界面附近的残基结合。我们发现糖基化对BRA的结合没有影响，因为所提出的结合位点远离任何聚糖。因此，我们的结果表明[植物名称未给出]可能是一种有前景的COVID-19预防和治疗替代药物。
