Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes COVID-19 which is responsible for respiratory illness infection in humans. The virus was first identified in China in 2019 and later spread to other countries worldwide. This study aims to identify the bioactive compounds from mangosteen (Garcinia mangostana L.) as an antiviral agent via dual inhibitor mechanisms against two SARS-CoV-2 proteases through the in silico approach. The three-dimensional structure of various bioactive compounds of mangosteen from the database was examined. Furthermore, all the target compounds were analyzed for drug, antiviral activity prediction, virtual screening, molecular interactions, and threedimensional structure visualization. It aimed to determine the potential of the bioactive compounds from mangosteen that can serve as antiviral agents to fight SARS-CoV-2. Results showed that the bioactive compounds from mangosteen have the prospective to provide antiviral agents that contradict the virus via dual inhibitory mechanisms. In summary, the binding of the various bioactive compounds from mangosteen results in low binding energy and is expected to have the ability to induce any activity of the target protein binding reaction. Therefore, it allows various bioactive compounds from mangosteen to act as dual inhibitory mechanisms for COVID-19 infection.

Introduction:To date, no specific therapeutic drug has been approved to target SARS-CoV-2. Hence, it remains a major challenge to decide what potential therapeutic regimens to treat COVID-19 patients. This study aims to investigate curcumin and virgin coconut oil (VCO) effects on cytokine levels (IL-1β, IL-2, IL-6, IL-18, TNF-α, and IFN-β) in COVID-19 patients. Methods: This study was a single-center, controlled trial with a parallel Arm or a Randomized Clinical trial design. A total of sixty COVID-19 patients admitted to the Universitas Sebelas Maret Hospital, Surakarta, Indonesia, were divided into two groups. The first group, consisting of 30 patients, was treated with Azithromycin 500 mg + Oseltamivir 2×75 mg + Hydroxychloroquine 400 mg/day for 5 days. The second group, comprising 30 patients, was treated with Azithromycin 500 mg + Oseltamivir 2×75 mg + Hydroxychloroquine 400 mg/day for 5 days, added with VCO 30 mL and curcumin 3×1 g/day for 21 days. The cytokine profiles of the serum samples were analyzed by the enzyme-linked immunosorbent assay (ELISA) on days 1, 14, and 21. Results: Our study showed that the second group had a significant reduction in IL-1β, IL-2, IL-6, TNF-α, and IFN-β levels after being treated with standard therapy added with curcumin and VCO on day 21 (p<0.05). Conclusion: These results suggested that curcumin and VCO might benefit the treatment of COVID-19 patients.