Linoleic acid for COVID-19

Linoleic acid may be beneficial for COVID-19 according to the studies below. COVID-19 involves the interplay of 400+ viral and host proteins and factors providing many therapeutic targets. Scientists have proposed 11,000+ potential treatments. c19early.org analyzes 210+ treatments. We have not reviewed linoleic acid in detail.
Dalisay et al., Marine Streptomyces-Derived Lipids Inhibit SARS-CoV-2 3CLpro Through In Vitro and Predicted Multi-Site Binding Mechanisms, Pharmaceuticals, doi:10.3390/ph19020294
Background: The SARS-CoV-2 3CLpro is essential for viral replication and an attractive target for antiviral intervention. While most strategies target the catalytic site, recent studies suggest that the dimerization interface and cryptic allosteric pockets offer alternative mechanisms for inhibition. Objective: This study investigated lipid metabolites from the marine sediment-derived Streptomyces sp. DSD454T as potential multi-site 3CLpro inhibitors. Methods: Metabolites were extracted from cultured biomass and characterized using LCMS-QTOF, MS/MS (LCMS-TQ), and 1H NMR, with identities confirmed against authentic standards. 3CLpro inhibition was assessed using a FRET-based assay, and ligand–protein interactions were evaluated through molecular docking and MM/GBSA calculations. Lipid content and comparative lipidomic signatures were examined across bioactive Streptomyces strains through LCMS-TQ and BODIPYTM 493/503 staining. Results: Palmitoleic and linoleic acids were identified as major constituents and inhibited SARS-CoV-2 3CLpro with IC50 values of 1.59 µg/mL (6.25 µM) and 5.29 µg/mL (18.88 µM). Molecular docking predicted that both fatty acids bind not only to the catalytic site but also to the dimerization interface and cryptic allosteric pocket. Additional lipids, including 9-heptadecenoic acid, linolenic acid, 9-HODE, and monoacylglycerols such as aggrecerides A–C and glyceryl-based lipids, showed similarly favorable multi-site binding profiles. Streptomyces sp. DSD454T also exhibited substantial lipid accumulation (~63% of crude extract). Across bioactive Streptomyces strains, a conserved lipid signature correlated strongly with 3CLpro inhibition. Conclusions: This study highlights the potential of microbial lipids as promising scaffolds for developing catalytic and allosteric SARS-CoV-2 3CLpro inhibitors and underscore marine Streptomyces as a valuable source of structurally simple yet mechanistically versatile antiviral metabolites.
Liu et al., Elucidation of anti-SARS-CoV-2 and anti-inflammatory bioactives in Qingyan Dropping Pills via integrated in silico screening and bioactivity validation, Frontiers in Medicine, doi:10.3389/fmed.2025.1684713
Background The global outbreak of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised significant public health concerns. Qingyan Dropping Pills (QDP), as a recommended drug, is issued by the National Health Commission of the People’s Republic of China for the treatment of COVID-19. However, its bioactive compounds and their mechanisms of action remain largely unidentified. In this study, the integration of computational and experimental approaches was performed to identify the bioactive compounds in QDP and elucidate its mechanisms against COVID-19. Methods Utilizing UPLC-Q/TOF-MS, the chemical compounds of QDP were delineated, followed by network pharmacology analysis and molecular docking targeting SARS-CoV-2 spike protein (S pro ), main protease (M pro ), and papain-like protease (PL pro ). To validate the inhibitory activity of these compounds, fluorescence resonance energy transfer (FRET) and surface plasmon resonance (SPR) assays were employed. The antivival efficacy was tested in Vero E6 cells infected with SARS-CoV-2 Omicron BA.5 variant. Moreover, anti-inflammatory potential was evaluated via the measurement of inflammatory markers, including nitric oxide (NO), interleukin-6 (IL-6), interleukin-1 beta (IL-1 β ), and tumor necrosis factor-alpha (TNF- α ). Results Among the 48 identified compounds, 33 demonstrated potential antiviral activity against COVID-19. Notably, Hamamelitannin (HAM), corilagin (COR), and rhoifolin (RHO) effectively interacted with S pro , M pro and PL pro in silico . In SPR assays, the equilibrium dissociation constant ( K D ) for COR and RHO ranged from 4.515 × 10 −8 M to 7.718 × 10 −6 M, while HAM showed strong binding affinity to S pro ( K D = 9.33 × 10 −8 M) but weaker affinity for M pro and PL pro . In FRET assays, COR and RHO inhibited..
García-Marín et al., Exploring SARS-CoV-2 Spike RBD Pockets as Targets for Generic Drugs: A Combined Computational, Biophysical, and Biological Approach, ACS Omega, doi:10.1021/acsomega.5c05175
Okechukwu et al., Marine-Derived Bioactive Metabolites as a Potential Therapeutic Intervention in Managing Viral Diseases: Insights from the SARS-CoV-2 In Silico and Pre-Clinical Studies, Pharmaceuticals, doi:10.3390/ph17030328
Worldwide urbanization and subsequent migration have accelerated the emergence and spread of diverse novel human diseases. Among them, diseases caused by viruses could result in epidemics, typified by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which hit the globe towards the end of December 2019. The global battle against SARS-CoV-2 has reignited interest in finding alternative treatments for viral infections. The marine world offers a large repository of diverse and unique bioactive compounds. Over the years, many antiviral compounds from marine organisms have been isolated and tested in vitro and in vivo. However, given the increasing need for alternative treatment, in silico analysis appears to provide a time- and cost-effective approach to identifying the potential antiviral compounds from the vast pool of natural metabolites isolated from marine organisms. In this perspective review, we discuss marine-derived bioactive metabolites as potential therapeutics for all known disease-causing viruses including the SARS-CoV-2. We demonstrate the efficacy of marine-derived bioactive metabolites in the context of various antiviral activities and their in silico, in vitro, and in vivo capacities.
Mehyar, N., Coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 helicase inhibitors: A systematic review of in vitro studies, Journal of Virus Eradication, doi:10.1016/j.jve.2023.100327
Abou Baker et al., An overview on medicinal plants used for combating coronavirus: Current potentials and challenges, Journal of Agriculture and Food Research, doi:10.1016/j.jafr.2023.100632
Ali et al., Computational Prediction of Nigella sativa Compounds as Potential Drug Agents for Targeting Spike Protein of SARS-CoV-2, Pakistan BioMedical Journal, doi:10.54393/pbmj.v6i3.853
SARS-CoV-2 was first identified in Wuhan, China in December 2019 and has rapidly devastated worldwide. The lack of approved therapeutic drugs has intensified the global situation, so researchers are seeking potential treatments using regular drug agents and traditional herbs as well. Objectives: To identify new therapeutic agents from Nigella sativa against spike protein (PDB ID: 7BZ5) of SARS-CoV-2. Methods: The 46 compounds from N. sativa were docked with spike protein using Molecular Operating Environment (MOE) software and compared with commercially available anti-viral drugs e.g., Arbidol, Favipiravir, Remdesivir, Nelfinavir, Chloroquine, Hydroxychloroquine. The Molecular Dynamic Simulation (MDS) analysis was also applied to determine ligand-protein complex stability. Furthermore, the pharmacological properties of compounds were also analyzed using AdmetSAR and SwissADME. Results: Out of its total 46 ligands, 8 compounds i.e., Methyl stearate, Eicosadienoic acid, Oleic acid, Stearic acid, Linoleic acid, Myristoleic acid, Palmitic acid, and Farnesol were selected for further analysis based on their minimum binding energy ranges from -7.45 to -7.07 kcal/mol. The docking scores of N. sativa phytocompounds were similar to drugs taken as control. Moreover, post simulation analysis of Methyl stearate complex predicted the most stable conformer. Conclusions: Further, in-vivo experiments are suggested to validate the medicinal use of Methyl stearate as potential inhibitors against spike protein of SARS-CoV-2.