Abstract Objective: Patients with coronavirus disease 2019 (COVID-19) experience various symptoms such as fever, cough, fatigue, and headache. At present, only two traditional over-the-counter medications, acetaminophen, and ibuprofen, are recommended for treating COVID-19 symptoms. However, there is an urgent need to discover safer remedies, potentially found in daily food items, that can be used for long-term prevention of COVID-19 symptoms. This study aimed to explore safe natural products capable of alleviating COVID-19 symptoms. Materials and Methods: We developed a Transcriptome-based Functional Gene Module Reference (TFGMR) approach, utilizing gene expression data from natural products and gene modules associated with COVID-19. Our hypothesis was that candidate natural products would significantly inhibit the expression of genes linked to COVID-19 symptoms without enhancing the expression of genes related to severe acute respiratory syndrome coronavirus 2 invasion. Results: Using the TFGMR approach, we identified 109 natural products with the potential to alleviate COVID-19 symptoms, with 15 of them having experimental evidence supporting their efficacy. These natural products consist of three daily food items – olive oil, nuts, and a mixture of vegetables, fruits, and yogurt; 43 functional foods, such as Fructus Gardeniae and Flos Lonicerae; as well as 63 natural drugs such as Plantamajoside and Safflomin A. These findings suggest that incorporating these three daily food items into one’s diet may contribute to the prevention of COVID-19. Conclusion: The study underscores the importance of recommending functional foods based on robust scientific evidence supporting their efficacy. The integration of diverse technological approaches holds promise in identifying safe remedies that could aid in the prevention and alleviation of COVID-19 symptoms, providing new opportunities for their everyday use.
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