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1.
Eur Rev Med Pharmacol Sci ; 25(21): 6741-6744, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1524862

ABSTRACT

OBJECTIVE: Coronaviruses are large, enveloped, positive-stranded RNA viruses. These viruses contain spike-like projections of glycoprotein on their surface, which appear like a crown. Millions of infections and thousands of deaths have been reported worldwide to date. Hence, the objective of the present study was to look for in silico evaluation of certain commercially available flavonoids against SARS-CoV-2 enzyme. MATERIALS AND METHODS: The in silico docking calculations were carried out using AutoDock 4.2 software. For the computational investigation, Apigenin, Catechin, Galangin, Luteolin, Naringenin were selected. An anti-viral drug Remdesivir was selected as reference drug. RESULTS: In the present study we found that Naringenin showed excellent binding score with the SARS-CoV-2 enzyme compared to the reference drug and other selected flavonoids. CONCLUSIONS: Based on the docking results, we conclude that Naringenin can be considered worthwhile to check its antiviral activity for the management of Coronavirus disease.


Subject(s)
Antiviral Agents/chemistry , Molecular Docking Simulation , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Antiviral Agents/metabolism , Binding Sites , COVID-19/pathology , COVID-19/virology , Catechin/chemistry , Catechin/metabolism , Flavanones/chemistry , Flavanones/metabolism , Flavonoids/chemistry , Flavonoids/metabolism , Humans , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/metabolism
2.
Molecules ; 26(21)2021 Nov 08.
Article in English | MEDLINE | ID: covidwho-1512511

ABSTRACT

This work describes an untargeted analytical approach for the screening, identification, and characterization of the trans-epithelial transport of green tea (Camellia sinensis) catechin extracts with in vitro inhibitory effect against the SARS-CoV-2 papain-like protease (PLpro) activity. After specific catechin extraction, a chromatographic separation obtained six fractions were carried out. The fractions were assessed in vitro against the PLpro target. Fraction 5 showed the highest inhibitory activity against the SARS-CoV-2 PLpro (IC50 of 0.125 µg mL-1). The untargeted characterization revealed that (-)-epicatechin-3-gallate (ECG) was the most abundant compound in the fraction and the primary molecule absorbed by differentiated Caco-2 cells. Results indicated that fraction 5 was approximately 10 times more active than ECG (IC50 value equal to 11.62 ± 0.47 µg mL-1) to inhibit the PLpro target. Overall, our findings highlight the synergistic effects of the various components of the crude extract compared to isolated ECG.


Subject(s)
Catechin/pharmacology , Coronavirus Papain-Like Proteases/metabolism , Tea/metabolism , Antiviral Agents/chemistry , COVID-19/drug therapy , COVID-19/metabolism , Caco-2 Cells , Camellia sinensis/metabolism , Catechin/analogs & derivatives , Catechin/chemistry , Catechin/metabolism , Coronavirus Papain-Like Proteases/drug effects , Epithelium/drug effects , Epithelium/metabolism , Humans , Mass Spectrometry/methods , Plant Extracts/chemistry , Plant Extracts/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Tea/chemistry , Tea/physiology
3.
Sci Rep ; 11(1): 2043, 2021 01 21.
Article in English | MEDLINE | ID: covidwho-1042518

ABSTRACT

The recent outbreak of the coronavirus (SARS-CoV2) is an unprecedented threat to human health and society across the globe. In this context, development of suitable interventions is the need of the hour. The viral spike protein (S Protein) and the cognate host cell receptor ACE2 can be considered as effective and appropriate targets for interventions. It is evident from the present computational study, that catechin and curcumin, not only exhibit strong binding affinity to viral S Protein and host receptor ACE2 but also to their complex (receptor-binding domain (RBD) of the spike protein of SARS-CoV2 and ACE2; RBD/ACE2-complex). The binding affinity values of catechin and curcumin for the S protein, ACE2 and RBD/ACE2-complex are - 10.5 and - 7.9 kcal/mol; - 8.9 and - 7.8 kcal/mol; and - 9.1 and - 7.6 kcal/mol, respectively. Curcumin directly binds to the receptor binding domain (RBD) of viral S Protein. Molecular simulation study over a period of 100 ns further substantiates that such interaction within RBD site of S Protein occurs during 40-100 ns out of 100 ns simulation trajectory. Contrary to this, catechin binds with amino acid residues present near the RBD site of S Protein and causes fluctuation in the amino acid residues of the RBD and its near proximity. Both catechin and curcumin bind the interface of 'RBD/ACE2-complex' and intervene in causing fluctuation of the alpha helices and beta-strands of the protein complex. Protein-protein interaction studies in presence of curcumin or catechin also corroborate the above findings suggesting the efficacy of these two polyphenols in hindering the formation of S Protein-ACE2 complex. In conclusion, this computational study for the first time predicts the possibility of above two polyphenols for therapeutic strategy against SARS-CoV2.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Catechin/metabolism , Curcumin/metabolism , SARS-CoV-2/drug effects , Spike Glycoprotein, Coronavirus/metabolism , Amino Acid Sequence , Angiotensin-Converting Enzyme 2/chemistry , Binding Sites , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/virology , Catechin/chemistry , Catechin/pharmacology , Cell Membrane/metabolism , Computational Biology/methods , Curcumin/chemistry , Curcumin/pharmacology , Humans , Molecular Docking Simulation , Protein Binding , Protein Domains , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry
4.
Drug Dev Res ; 82(1): 86-96, 2021 02.
Article in English | MEDLINE | ID: covidwho-696175

ABSTRACT

SARS-CoV-2 or COVID-19 pandemic global outbreak created the most unstable situation of human health-economy. In the past two decades different parts of the word experienced smaller or bigger outbreak related to human coronaviruses. The spike glycoproteins of the COVID-19 (similar to SARS-CoV) attach to the angiotensin-converting enzyme (ACE2) and transit over a stabilized open state for the viral internalization to the host cells and propagate with great efficacy. Higher rate of mutability makes this virus unpredictable/less sensitive to the protein/nucleic acid based drugs. In this emergent situation, drug-induced destabilization of spike binding to RBD could be a good strategy. In the current study we demonstrated by bioinformatics (CASTp: computed atlas of surface topography of protein, PyMol: molecular visualization) and molecular docking (PatchDock and Autodock) experiments that tea flavonoids catechin products mainly epigallocatechin gallate or other like theaflavin gallate demonstrated higher atomic contact energy (ACE) value, binding energy, Ki value, ligand efficiency, surface area and more amino acid interactions than hydroxychloroquine (HCQ) during binding in the central channel of the spike protein. Moreover, out of three distinct binding sites (I, II and III) of spike core when HCQ binds only with site III (farthest from the nCoV-RBD of ACE2 contact), epigallocatechin gallate and theaflavin gallate bind all three sites. As sites I and II are in closer contact with open state location and viral-host contact area, these drugs might have significant effects. Taking into account the toxicity/side effects by chloroquine/HCQ, present drugs may be important. Our laboratory is working on tea flavonoids and other phytochemicals in the protection from toxicity, DNA/mitochondrial damage, inflammation and so on. The present data might be helpful for further analysis of flavonoids in this emergent pandemic situation.


Subject(s)
Biflavonoids/metabolism , Catechin/analogs & derivatives , Computational Biology/methods , Gallic Acid/analogs & derivatives , Hydroxychloroquine/metabolism , Molecular Docking Simulation/methods , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Biflavonoids/chemistry , Binding Sites/physiology , COVID-19/metabolism , Catechin/chemistry , Catechin/metabolism , Gallic Acid/chemistry , Gallic Acid/metabolism , Humans , Hydroxychloroquine/chemistry , Protein Structure, Secondary , Protein Structure, Tertiary , Spike Glycoprotein, Coronavirus/chemistry , X-Ray Diffraction/methods
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