Boosting Immunity: Synergistic Antiviral Effects of Luteolin, Vitamin C, Magnesium, and Zinc Against SARS-CoV-2 3CLpro
Juliana C Ferreira, Samar Fadl, Thyago H S Cardoso, Bruno Silva Andrade, Tarcisio S Melo, Edson Mario De, Andrade Silva, Anupriya Agarwal, Stuart J Turville, Nitin K Saksena, Wael M Rabeh
doi:10.1042/BSR20240617/959341/bsr-2024
SARS-CoV-2 was first discovered in 2019 and has disseminated throughout the globe to pandemic levels, imposing significant health and economic burdens. Although vaccines against SARS-CoV-2 have been developed, their long-term efficacy and specificity have not been determined, and antiviral drugs remain necessary. Flavonoids, which are commonly found in plants, fruits, and vegetables and are part of the human diet, have attracted considerable attention as potential therapeutic agents due to their antiviral and antimicrobial activities and effects on other biological activities, such as inflammation. This study uses a combination of biochemical, cellular, molecular dynamics, and molecular docking experiments to provide compelling evidence that the flavonoid luteolin (2-(3,4-Dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4one) has antiviral activity against SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) that is synergistically enhanced by magnesium, zinc, and vitamin C. The IC 50 of luteolin against 2 µM 3CLpro is 78 µM and decreases 10-fold to 7.6 µM in the presence of zinc, magnesium, and vitamin C. Thermodynamic stability analyses revealed that luteolin has minimal effects on the structure of 3CLpro, whereas metal ions and vitamin C significantly alter the thermodynamic stability of the protease. Interactome analysis uncovered potential host-virus interactions and functional clusters associated with luteolin activity, supporting the relevance of this flavone for combating SARS-CoV-2 infection. This comprehensive investigation sheds light on luteolin's therapeutic potential and provides insights into its mechanisms of action against SARS-CoV-2. The novel formulation of luteolin, magnesium, zinc, and vitamin C may be an effective avenue for treating COVID-19 patients.
This research was partially carried out using the Core Technology Platforms resources at New York University Abu Dhabi.
Conflict of Interest JF, TC, NS, and WR are part of a US provisional patent application filed by New York University Abu Dhabi and ProPhase Labs.
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