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All Studies   Meta Analysis    Recent:   

Potential In Vitro Inhibition of Selected Plant Extracts against SARS-CoV-2 Chymotripsin-Like Protease (3CLPro) Activity

Guijarro-Real et al., Foods, doi:10.3390/foods10071503
Jun 2021  
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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 75 treatments. c19early.org
In Vitro study of several plant extracts, showing strong inhibition of SARS-CoV-2 3CLpro activity by turmeric rhizomes. Commercial curcumin also inhibited 3CLpro activity, but did not fully account for the inhibitory effect of turmeric rhizomes extracts, suggesting that other components of the turmeric extract also play a main role in inhibiting 3CLpro activity.
43 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,17,9,20,11,4 (and specifically the receptor binding domainB,7,13,10), MproC,9,20,13,8,21,18,23,6,15,12,33,10,4, RNA-dependent RNA polymeraseD,19,10, ACE2E,11,12,14, nucleocapsidF,5,22, and nsp10G,22 proteins. In Vitro studies demonstrate inhibition of the spikeA,28 (and specifically the receptor binding domainB,36), MproC,33,35,28,16, ACE2E,36, and TMPRSS2H,36 proteins. In Vitro studies demonstrate efficacy in Calu-3I,34, A549J,28, 293TK,1, HEK293-hACE2L,26,16, 293T/hACE2/TMPRSS2M,27, Vero E6N,34,10,20,30,28,26,6,29,32, and SH-SY5YO,25 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 variants7, decreases pro-inflammatory cytokines induced by SARS-CoV-2 in peripheral blood mononuclear cells32, and alleviates SARS-CoV-2 spike protein-induced mitochondrial membrane damage and oxidative stress1.
Guijarro-Real et al., 29 Jun 2021, peer-reviewed, 5 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperCurcuminAll
Potential In Vitro Inhibition of Selected Plant Extracts against SARS-CoV-2 Chymotripsin-Like Protease (3CLPro) Activity
Carla Guijarro-Real, Mariola Plazas, Adrián Rodríguez-Burruezo, Jaime Prohens, Ana Fita
Foods, doi:10.3390/foods10071503
Antiviral treatments inhibiting Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication may represent a strategy complementary to vaccination to fight the ongoing Coronavirus disease 19 (COVID-19) pandemic. Molecules or extracts inhibiting the SARS-CoV-2 chymotripsin-like protease (3CL Pro ) could contribute to reducing or suppressing SARS-CoV-2 replication. Using a targeted approach, we identified 17 plant products that are included in current and traditional cuisines as promising inhibitors of SARS-CoV-2 3CL Pro activity. Methanolic extracts were evaluated in vitro for inhibition of SARS-CoV-2 3CL Pro activity using a quenched fluorescence resonance energy transfer (FRET) assay. Extracts from turmeric (Curcuma longa) rhizomes, mustard (Brassica nigra) seeds, and wall rocket (Diplotaxis erucoides subsp. erucoides) at 500 µg mL −1 displayed significant inhibition of the 3CL Pro activity, resulting in residual protease activities of 0.0%, 9.4%, and 14.9%, respectively. Using different extract concentrations, an IC 50 value of 15.74 µg mL −1 was calculated for turmeric extract. Commercial curcumin inhibited the 3CL Pro activity, but did not fully account for the inhibitory effect of turmeric rhizomes extracts, suggesting that other components of the turmeric extract must also play a main role in inhibiting the 3CL Pro activity. Sinigrin, a major glucosinolate present in mustard seeds and wall rocket, did not have relevant 3CL Pro inhibitory activity; however, its hydrolysis product allyl isothiocyanate had an IC 50 value of 41.43 µg mL −1 . The current study identifies plant extracts and molecules that can be of interest in the search for treatments against COVID-19, acting as a basis for future chemical, in vivo, and clinical trials.
This work is a first targeted approach for the evaluation of plant extracts and containing natural compounds for the development of prophylaxis, adjuvant therapies, and drug treatments aimed at inhibiting the activity of SARS-CoV-2 3CL Pro . Extracts of turmeric have been identified as a candidate plant extract for reducing SARS-CoV-2 3CL Pro activity, which could eventually affect the viral replication. In addition, other plant extracts, such as those of cruciferous plants containing sinigrin, which, after consumption, is degraded to allyl isothiocyanate, might be considered as well for their inhibition of SARS-CoV-2 3CL Pro activity. The current study provides information that can help in the search for treatments against COVID-19, acting as a basis for future chemical, in vivo, and clinical trials. Thus, further studies following the results of this work should be addressed: (1) to chemically characterize the plant extracts with high potential inhibitory activity and to re-evaluate this capacity after the fractionation of the extracts, thus allowing the identification of the biomolecules responsible of such activity and possible synergistic effects; and (2) to evaluate this potential inhibition in cell-based studies where the virus, host cell, and plant extract interact, also determining the toxicity limit prior to conducting other pre-clinical and clinical trials. Supplementary Materials: The following are available online at https://www.mdpi.com/article/..
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Using a targeted approach, we identified 17 plant products that are ' 'included in current and traditional cuisines as promising inhibitors of SARS-CoV-2 3CLPro ' 'activity. Methanolic extracts were evaluated in vitro for inhibition of SARS-CoV-2 3CLPro ' 'activity using a quenched fluorescence resonance energy transfer (FRET) assay. Extracts from ' 'turmeric (Curcuma longa) rhizomes, mustard (Brassica nigra) seeds, and wall rocket ' '(Diplotaxis erucoides subsp. erucoides) at 500 µg mL−1 displayed significant inhibition of ' 'the 3CLPro activity, resulting in residual protease activities of 0.0%, 9.4%, and 14.9%, ' 'respectively. Using different extract concentrations, an IC50 value of 15.74 µg mL−1 was ' 'calculated for turmeric extract. Commercial curcumin inhibited the 3CLPro activity, but did ' 'not fully account for the inhibitory effect of turmeric rhizomes extracts, suggesting that ' 'other components of the turmeric extract must also play a main role in inhibiting the 3CLPro ' 'activity. Sinigrin, a major glucosinolate present in mustard seeds and wall rocket, did not ' 'have relevant 3CLPro inhibitory activity; however, its hydrolysis product allyl ' 'isothiocyanate had an IC50 value of 41.43 µg mL−1. The current study identifies plant ' 'extracts and molecules that can be of interest in the search for treatments against COVID-19, ' 'acting as a basis for future chemical, in vivo, and clinical trials.</jats:p>', 'DOI': '10.3390/foods10071503', 'type': 'journal-article', 'created': {'date-parts': [[2021, 6, 29]], 'date-time': '2021-06-29T14:52:46Z', 'timestamp': 1624978366000}, 'page': '1503', 'source': 'Crossref', 'is-referenced-by-count': 28, 'title': 'Potential In Vitro Inhibition of Selected Plant Extracts against SARS-CoV-2 Chymotripsin-Like ' 'Protease (3CLPro) Activity', 'prefix': '10.3390', 'volume': '10', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-8015-1559', 'authenticated-orcid': False, 'given': 'Carla', 'family': 'Guijarro-Real', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-8090-7312', 'authenticated-orcid': False, 'given': 'Mariola', 'family': 'Plazas', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Adrián', 'family': 'Rodríguez-Burruezo', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-1181-9065', 'authenticated-orcid': False, 'given': 'Jaime', 'family': 'Prohens', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-8637-5852', 'authenticated-orcid': False, 'given': 'Ana', 'family': 'Fita', 'sequence': 'additional', 'affiliation': []}], 'member': '1968', 'published-online': {'date-parts': [[2021, 6, 29]]}, 'reference': [ {'key': 'ref1', 'doi-asserted-by': 'publisher', 'DOI': '10.1021/acs.molpharmaceut.0c00608'}, { 'key': 'ref2', 'unstructured': 'Coronavirus Disease (COVID-19) Weekly Epidemiological Update and Weekly ' 'Operational Update. 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