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All Studies   Meta Analysis    Recent:   

Thermal shift assay (TSA)-based drug screening strategy for rapid discovery of inhibitors against the Nsp13 helicase of SARS-CoV-2

Li et al., Animals and Zoonoses, doi:10.1016/j.azn.2024.06.001
Jul 2024  
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Curcumin for COVID-19
15th treatment shown to reduce risk in February 2021
 
*, now with p = 0.0000000096 from 27 studies.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 81 treatments. c19early.org
In Vitro study showing that 11 compounds inhibited the SARS-CoV-2 helicase Nsp13, with 7 compounds inhibiting ATPase activity and 4 inhibiting RNA unwinding activity at micromolar concentrations. Authors screened 1,970 FDA-approved drugs using a thermal shift assay, identifying 26 top binders to Nsp13. Biochemical assays confirmed 7 ATPase inhibitors (verteporfin, olsalazine sodium, diclofenac, benidipine, dyclonine, methyl salicylate, butylparaben; IC50 1.07-6.55 μM) and 4 RNA unwinding inhibitors (efaproxiral, fenretinide, curcumin, wedelolactone; IC50 12.23-14.91 μM). The inhibitors were reversible and docking predicted binding to Nsp13's ATPase or RNA binding domains. Curcumin was the most promising helicase inhibitor identified.
45 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,5,10,12,18,21 (and specifically the receptor binding domainB,8,11,14), MproC,5,7,9-11,13,14,16,19,21,22,24,35, RNA-dependent RNA polymeraseD,11,20, ACE2E,12,13,15, nucleocapsidF,6,23, nsp10G,23, and helicaseH,25 proteins. In Vitro studies demonstrate inhibition of the spikeA,30 (and specifically the receptor binding domainB,38), MproC,17,30,35,37, ACE2E,38, and TMPRSS2I,38 proteins. In Vitro studies demonstrate efficacy in Calu-3J,36, A549K,30, 293TL,1, HEK293-hACE2M,17,28, 293T/hACE2/TMPRSS2N,29, Vero E6O,7,11,21,28,30-32,34,36, and SH-SY5YP,27 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 cells34, and alleviates SARS-CoV-2 spike protein-induced mitochondrial membrane damage and oxidative stress1.
Li et al., 1 Jul 2024, China, peer-reviewed, 4 authors. Contact: cryptosporida@gmail.com (corresponding author).
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperCurcuminAll
Thermal shift assay (TSA)-based drug screening strategy for rapid discovery of inhibitors against the Nsp13 helicase of SARS-CoV-2
Meng Li, Jigang Yin, Chang Li, Guan Zhu
Animals and Zoonoses, doi:10.1016/j.azn.2024.06.001
Thermal shift assay (TSA)-based drug screening strategy for rapid discovery of inhibitors against the Nsp13 helicase of SARS
CRediT authorship contribution statement Meng Li played a key role in the experimental setup and data collection, and were responsible for ensuring the quality and integrity of the data obtained. In addition, Meng Li contributed to the analysis J o u r n a l P r e -p r o o f Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author Guan Zhu and Chang Li are Editorial Board Member for Animals and Zoonoses and were not involved in the editorial review or the decision to publish this article. Declaration of interests ☐ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. J o u r n a l P r e -p r o o f
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