Beta-sitosterol for COVID-19

Since the coronavirus disease 2019 (COVID-19) outbreak, although have controlled, severe acute respiratory syndrome coronavirus 2 is constantly mutating and affects people’s health. FDA has approved Paxlovid and Molnupiravir for COVID-19 treatment, however, they have not been approved for children under 12 years old. Therefore, it is urgent to explore new drugs for treating COVID-19 in children. As a traditional Chinese medicine, Qing Yan He Ji (QYHJ) has been widely used as an antiviral in our hospital. Therefore, we presumed that it may be ideal for treating COVID-19 and explored its therapeutic effect in patients with COVID-19. The targets and underlying mechanisms of QYHJ against COVID-19 in children were investigated using bioinformatics. QYHJ target sets, and related target genes of COVID-19 were retrieved from public databases. Subsequently, gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to investigate the potential mechanism of QYHJ against COVID-19. Finally, molecular docking was carried out to analyze the affinity between the effective molecule and the target protein. A total of 15 bioactive ingredients of QYHJ and 111 predicted potential targets of QYHJ against COVID-19 were screened. A protein–protein interaction network and subnetworks identified 21 core target genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that QYHJ functions against COVID-19 primarily through antiviral and anti-inflammatory effects. Molecular docking of interleukin-6 (IL-6) revealed that 5 active compounds had relatively stable binding activities with IL-6. Molecular dynamics simulation was performed for molecular docking results, showing IL-6–(4aS,6aR,6aS,6bR,8aR,10R,12aR,14bS)-10-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid (4aS) complex, IL-6–stigmasterol complex, IL-6–poriferasterol complex, IL-6–sitosterol complex, and IL-6–beta-sitosterol complex had relatively good binding stability. In conclusion, the multi-component and multi-target intervention of QYHJ against COVID-19 is closely related to antiviral and anti-inflammatory activities, which provides a theoretical basis for clinical application.

<ns3:p>Background Although the COVID-19 pandemic has diminished in intensity, the virus continues to circulate globally. The SARS-CoV-2 main protease (Mpro) is a key enzyme in the life cycle of the virus, making it important for the development of treatments against future variants of the virus. In this work, Peruvian natural compounds were evaluated against different mutations of the SARS-CoV-2 Mpro. Methods In silico techniques such as virtual screening, all-atom molecular dynamics simulations, and energy estimation analysis were applied. Results Of the tested compounds by virtual screening, rutin was identified as the best binding agent against the different proposed Mpro mutations. In addition, computational simulations and energy estimation analysis demonstrated the high structural and energetic stability between the Mpro-rutin systems. Conclusions Overall, our study identified rutin as the most promising compound with a strong affinity for various Mpro mutations, potentially playing a key role in the development of new treatments for emerging viral variants.</ns3:p>