Porphyrin-derived carbon dots for an enhanced antiviral activity targeting the CTD of SARS-CoV-2 nucleocapsid.

IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal, genetic engineering & biotechnology Pub Date : 2023-10-06 DOI:10.1186/s43141-023-00548-z
Azzania Fibriani, Audrey Angelina Putri Taharuddin, Nicholas Yamahoki, Rebecca Stephanie, Jessica Laurelia, Dian Fitria Agustiyanti, Popi Hadi Wisnuwardhani, Marissa Angelina, Yana Rubiyana, Ratih Asmana Ningrum, Andri Wardiana, Desriani Desriani, Ferry Iskandar, Fitri Aulia Permatasari, Ernawati Arifin Giri-Rachman
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Abstract

Background: Since effective antiviral drugs for COVID-19 are still limited in number, the exploration of compounds that have antiviral activity against SARS-CoV-2 is in high demand. Porphyrin is potentially developed as a COVID-19 antiviral drug. However, its low solubility in water restricts its clinical application. Reconstruction of porphyrin into carbon dots is expected to possess better solubility and bioavailability as well as lower biotoxicity.

Methods and results: In this study, we investigated the antiviral activity of porphyrin and porphyrin-derived carbon dots against SARS-CoV-2. Through the in silico analysis and assessment using a novel drug screening platform, namely dimer-based screening system, we demonstrated the capability of the antivirus candidates in inhibiting the dimerization of the C-terminal domain of SARS-CoV-2 Nucleocapsid. It was shown that porphyrin-derived carbon dots possessed lower cytotoxicity on Vero E6 cells than porphyrin. Furthermore, we also assessed their antiviral activity on the SARS-CoV-2-infected Vero E6 cells. The transformation of porphyrin into carbon dots substantially augmented its performance in disrupting SARS-CoV-2 propagation in vitro.

Conclusions: Therefore, this study comprehensively demonstrated the potential of porphyrin-derived carbon dots to be developed further as a promisingly safe and effective COVID-19 antiviral drug.

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卟啉衍生的碳点用于增强针对严重急性呼吸系统综合征冠状病毒2型核衣壳CTD的抗病毒活性。
背景:由于治疗新冠肺炎的有效抗病毒药物数量仍然有限,因此对具有抗SARS-CoV-2抗病毒活性的化合物的探索需求很大。卟啉有可能被开发为新冠肺炎抗病毒药物。然而,其在水中的低溶解度限制了其临床应用。将卟啉重建为碳点有望具有更好的溶解性和生物利用度以及更低的生物毒性。方法和结果:在本研究中,我们研究了卟啉和卟啉衍生的碳点对严重急性呼吸系统综合征冠状病毒2型的抗病毒活性。通过使用新型药物筛选平台,即基于二聚体的筛选系统进行的计算机分析和评估,我们证明了候选抗病毒药物抑制严重急性呼吸系统综合征冠状病毒2型核衣壳C端结构域二聚化的能力。结果表明,卟啉衍生的碳点对Vero E6细胞的细胞毒性低于卟啉。此外,我们还评估了它们对严重急性呼吸系统综合征冠状病毒2型感染的Vero E6细胞的抗病毒活性。卟啉转化为碳点大大增强了其在体外干扰严重急性呼吸系统综合征冠状病毒2型传播的性能。结论:因此,本研究全面展示了卟啉衍生碳点作为一种安全有效的新冠肺炎抗病毒药物的潜力。
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