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Computational Discovery of Mitochondrial Dysfunction Biomarkers in Severe SARS-CoV-2 Infection: Facilitating Pytomedicine Screening

Zhang et al., Phytomedicine, doi:10.1016/j.phymed.2024.155784
May 2024  
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Curcumin for COVID-19
14th treatment shown to reduce risk in February 2021
*, now with p = 0.000000015 from 26 studies.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,300+ studies for 77 treatments.
In Silico and In Vitro study showing potential benefits of curcumin for severe COVID-19 by protecting mitochondrial function and reducing dysregulated metabolism and immune response. Authors identified five mitochondrial dysfunction biomarkers (RECQL4, PYCR1, PIF1, POLQ, GLDC) that distinguish severe COVID-19 patients and regulate abnormal metabolism and immunity. In Silico screening of 496 natural compounds found curcumin had the highest potential to modulate these biomarkers. In Vitro, pre-treatment with curcumin for 8 hours alleviated SARS-CoV-2 S1 protein-induced mitochondrial membrane potential damage and reduced elevated reactive oxygen species levels in cells.
44 preclinical studies support the efficacy of curcumin for COVID-19:
In Silico studies predict inhibition of SARS-CoV-2 with curcumin or metabolites via binding to the spikeA,18,10,21,12,5 (and specifically the receptor binding domainB,8,14,11), MproC,10,21,14,9,22,19,24,7,16,13,34,11,5, RNA-dependent RNA polymeraseD,20,11, ACE2E,12,13,15, nucleocapsidF,6,23, and nsp10G,23 proteins. In Vitro studies demonstrate inhibition of the spikeA,29 (and specifically the receptor binding domainB,37), MproC,34,36,29,17, ACE2E,37, and TMPRSS2H,37 proteins. In Vitro studies demonstrate efficacy in Calu-3I,35, A549J,29, 293TK,1, HEK293-hACE2L,27,17, 293T/hACE2/TMPRSS2M,28, Vero E6N,35,11,21,31,29,27,7,30,33, and SH-SY5YO,26 cells. Curcumin is predicted to inhibit the interaction between the SARS-CoV-2 spike protein receptor binding domain and the human ACE2 receptor for the delta and omicron variants8, decreases pro-inflammatory cytokines induced by SARS-CoV-2 in peripheral blood mononuclear cells33, and alleviates SARS-CoV-2 spike protein-induced mitochondrial membrane damage and oxidative stress1.
Zhang et al., 31 May 2024, peer-reviewed, 10 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperCurcuminAll
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