In Silico study showing that the natural compounds kaempferol, quercetin, and rutin bind to the main protease (Mpro) of SARS-CoV-2, also known as 3CLpro, with high affinity. Authors find these flavonoids interact with active site residues His41 and Cys145 through hydrogen bonding and hydrophobic interactions at the substrate binding pocket. Notably, rutin's binding affinity was higher than reference drugs chloroquine, hydroxychloroquine and remdesivir.
68 preclinical studies support the efficacy of quercetin for COVID-19:
In Silico studies predict inhibition of SARS-CoV-2, or minimization of side effects, with quercetin or metabolites via binding to the spikeA,6,7,19,21,22,27,35,36,38,39,59,60, MproB,4,6,8,10,12,14,15,17,20,21,27,31,33-35,39,40,42,60,61, RNA-dependent RNA polymeraseC,6,29, PLproD,34,42, ACE2E,19,20,25,34,38,60, TMPRSS2F,19, helicaseG,26,31, endoribonucleaseH,36, NSP16/10I,3, cathepsin LJ,23, Wnt-3K,19, FZDL,19, LRP6M,19, ezrinN,37, ADRPO,35, NRP1P,38, EP300Q,13, PTGS2R,20, HSP90AA1S,13,20, matrix metalloproteinase 9T,28, IL-6U,18,32, IL-10V,18, VEGFAW,32, and RELAX,32 proteins.
In Vitro studies demonstrate inhibition of the MproB,12,43,48,56 protein, and inhibition of spike-ACE2 interactionY,44.
In Vitro studies demonstrate efficacy in Calu-3Z,47, A549AA,18, HEK293-ACE2+AB,55, Huh-7AC,22, Caco-2AD,46, Vero E6AE,16,39,46, mTECAF,49, and RAW264.7AG,49 cells.
Animal studies demonstrate efficacy in K18-hACE2 miceAH,52, db/db miceAI,49,58, BALB/c miceAJ,57, and rats62.
Quercetin reduced proinflammatory cytokines and protected lung and kidney tissue against LPS-induced damage in mice57, inhibits LPS-induced cytokine storm by modulating key inflammatory and antioxidant pathways in macrophages2, and inhibits SARS-CoV-2 ORF3a ion channel activity, which contributes to viral pathogenicity and cytotoxicity51.
{ 'indexed': {'date-parts': [[2021, 5, 12]], 'date-time': '2021-05-12T11:47:28Z', 'timestamp': 1620820048487},
'reference-count': 0,
'publisher': 'Bentham Science Publishers Ltd.',
'content-domain': {'domain': [], 'crossmark-restriction': False},
'short-container-title': ['CPD'],
'published-print': {'date-parts': [[2020, 11, 16]]},
'abstract': '<jats:sec>\n'
'<jats:title>Abstract::</jats:title>\n'
'<jats:p>The emergence and dissemination of SARS-CoV-2 has caused high mortality and enormous '
'economic loss. Rapid development of new drug molecules is the need of hour to fight COVID-19. '
'However, the conventional approaches of drug development are time consuming and expensive. '
'Here, we have adopted a computational approach to identify lead molecules from nature. '
'Ligands from natural compounds library available at Selleck Inc (L1400) have been screened '
'for their ability to bind and inhibit the main protease (3CLpro) of SARS-CoV-2. We found that '
'Kaempferol, Quercetin, and Rutin were bound at the substrate binding pocket of 3CLpro with '
'high affinity (105-106 M-1) and interact with the active site residues such as His41 and '
'Cys145 through hydrogen bonding and hydrophobic interactions. In fact, the binding affinity '
'of Rutin (~106 M-1) was much higher than Chloroquine (~103 M-1) and Hydroxychloroquine (~104 '
'M-1), and the reference drug Remdesivir (~105 M-1). The results suggest that natural '
'compounds such as flavonoids have the potential to be developed as novel inhibitors of '
'SARS-CoV-2 with a comparable/higher potency as that of Remdesivir. However, their clinical '
'usage on COVID-19 patients is a subject of further investigations and clinical '
'trials.</jats:p>\n'
'</jats:sec>',
'DOI': '10.2174/1381612826999201116195851',
'type': 'journal-article',
'created': { 'date-parts': [[2020, 11, 20]],
'date-time': '2020-11-20T09:56:49Z',
'timestamp': 1605866209000},
'source': 'Crossref',
'is-referenced-by-count': 2,
'title': [ 'Natural Compounds as Inhibitors of SARS-CoV-2 Main Protease (3CLpro): A Molecular Docking and '
'Simulation Approach to Combat COVID-19'],
'prefix': '10.2174',
'volume': '26',
'author': [ { 'given': 'Md Tabish',
'family': 'Rehman',
'sequence': 'first',
'affiliation': [ { 'name': 'Department of Pharmacognosy, College of Pharmacy, King Saud '
'University, Riyadh-11451,, Saudi Arabia'}]},
{ 'given': 'Mohamed F.',
'family': 'AlAjmi',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Pharmacognosy, College of Pharmacy, King Saud '
'University, Riyadh-11451,, Saudi Arabia'}]},
{ 'ORCID': 'http://orcid.org/0000-0001-9769-2557',
'authenticated-orcid': True,
'given': 'Afzal',
'family': 'Hussain',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Pharmacognosy, College of Pharmacy, King Saud '
'University, Riyadh-11451,, Saudi Arabia'}]}],
'member': '965',
'container-title': ['Current Pharmaceutical Design'],
'original-title': [],
'language': 'en',
'deposited': { 'date-parts': [[2020, 11, 20]],
'date-time': '2020-11-20T09:56:53Z',
'timestamp': 1605866213000},
'score': 1,
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2020, 11, 16]]},
'references-count': 0,
'alternative-id': ['LiveAll1'],
'URL': 'http://dx.doi.org/10.2174/1381612826999201116195851',
'relation': {},
'ISSN': ['1381-6128'],
'issn-type': [{'value': '1381-6128', 'type': 'print'}],
'subject': ['Drug Discovery', 'Pharmacology'],
'published': {'date-parts': [[2020, 11, 16]]}}
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