Anti-SARS-CoV-2 and anticancer properties of triptolide and its derived carbonized nanomaterials
Rubina Kousar, Tahira Akhtar, Chin‐Jung Lin, Timofey Lebedev, Yi‐Chuan Li, Chih-Chao Yang, Wei‐Jan Wang, Hsiao‐Fan Chen, Wen‐Chi Su, Pulak Kumar Biswas, Najm Us Saqib, Sefealem Assefa Belay, Tzu-Chi Chang, Da-Wei Guo, Qiang Li, Bbumba Patrick, Muhammad Usama, Chen-Shiou Wu, Wen-Lung Ma, Yuh‐Pyng Sher, Chih‐Ching Huang, Mien‐Chie Hung, Li X
Abstract
The COVID-19 pandemic remains an ongoing global health threat, yet effective treatments are still lacking. This has led to a high demand for complementary/alternative medicine, such as Chinese herbal medicines for curbing the COVID-19 pandemic. Given the dual anticancer and antiviral activities of many herbal drugs, they may hold a multifaceted potential to tackle both cancer and SARS-CoV-2. Triptolide is the major bioactive compound isolated from Tripterygium wilfordii Hook F (TwHF), a traditional Chinese medicinal herb recognized for its beneficial pharmacological properties in many diseases, including cancer and viral infection. However, its application in the clinic has been greatly limited due to its toxicity and poor water solubility. Here, from a screen of a natural compound library of Chinese Pharmacopoeia, we identified triptolide as a top candidate to inhibit cell entry of SARS-CoV-2. We demonstrated that triptolide robustly blocked viral entry at nanomolar concentrations in cellular models, with broad range activity against emerging Omicron variants of SARS-CoV-2. Mechanistically, triptolide disrupted the interaction of SARS-CoV-2 spike protein with its receptor ACE2. Furthermore, we synthesized water-soluble, triptolide-derived carbon quantum dots. Compared to triptolide, these highly biocompatible nanomaterials exhibited prominent antiviral capabilities against Omicron variants of SARS-CoV-2 with less cytotoxicity. Finally, we showed that triptolide-derived carbonized materials excelled in their anticancer properties compared to triptolide and Minnelide, a water-soluble analog of triptolide. Together, our results provide a rationale for the potential development of triptolide-carbonized derivatives as a promising antiviral candidate for the current pandemic and future outbreaks, as well as anticancer agents.