Black tea bioactives as inhibitors of multiple targets of SARS-CoV-2 (3CLpro, PLpro and RdRp): a virtual screening and molecular dynamic simulation study

Gogoi, Madhurjya; Borkotoky, Meghali; Borchetia, Sangeeta; Chowdhury, Pritom; Mahanta, Saurov; Barooah, Anoop Kumar

doi:10.1080/07391102.2021.1897679

Cited by 23 publications

(20 citation statements)

References 60 publications

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“… 91 The latest research has evidenced the capacity of procyanidins to significantly interact with SARS-CoV-2 3CL PRO , nsp1, nsp2, PL PRO , nsp4, nsp6, nsp7, nsp8, nsp9, nsp10, RdRp, helicase, exon N, NendoU, 2′-O-MT, ORF3a, E protein, M protein, ORF6, ORF7a, ORF8, N protein, ORF10, ACE2, and S protein. 84 , 87 , 92 Interestingly, flavan-3-ols and procyanidins were also associated with ACE inhibition in vitro . 93 These studies highlight the extension of the potential of flavanols (e.g.…”

Section: Natural Products Targeting Autophagy To Halt Cell-to-cell Virus Propagationmentioning

confidence: 97%

“… 82 , 83 , 84 Tea polyphenols, including epigallocatechin-3-O-gallate (EGCG) and theaflavin 3,3'di-gallate, can strongly dock to 3CL PRO , S protein, S/ACE2 complex, PL PRO , and RdRp. 85 , 86 , 87 Also, a computational analysis revealed that several compounds with a common catechin skeleton can inhibit SARS-CoV-2 protein N. 88 Altogether, these compounds could suppress the SARS-CoV-2 replication through the inhibition of viral proteins involved in DMV biogenesis and autophagy. However, green tea polyphenols have low bio-accessibility (90% is lost upon gastric and intestinal digestion) and low bioavailability.…”

Section: Natural Products Targeting Autophagy To Halt Cell-to-cell Virus Propagationmentioning

confidence: 99%

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Targeting autophagy with natural products to prevent SARS-CoV-2 infection

Vidoni

Fuzimoto

Ferraresi

et al. 2022

Journal of Traditional and Complementary Medicine

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Section: Natural Products Targeting Autophagy To Halt Cell-to-cell Virus Propagationmentioning

confidence: 97%

Section: Natural Products Targeting Autophagy To Halt Cell-to-cell Virus Propagationmentioning

confidence: 99%

Targeting autophagy with natural products to prevent SARS-CoV-2 infection

Vidoni

Fuzimoto

Ferraresi

et al. 2022

Journal of Traditional and Complementary Medicine

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“…Structure-based virtual screening (SBVS) of diverse ligand databases, many of them containing drug repurposing candidates and natural products, has been extensively applied to identify potential 3CL pro inhibitors (Wu C. et al, 2020;Chowdhury et al, 2020;Jukic et al, 2020;Meyer-Almes, 2020;Olubiyi et al, 2020;Selvaraj et al, 2020;Federico et al, 2021;Gogoi et al, 2021;Guedes et al, 2021;Kumar et al, 2021;Lokhande et al, 2021;Naik et al, 2021;Rajpoot et al, 2021;Rehman et al, 2021;Sisakht et al, 2021). In several cases, this approach has led to the successful identification of compounds displaying in vitro inhibitory activity against 3CL pro (Ghahremanpour et al, 2020;Gupta et al, 2020;Jin et al, 2020;Li et al, 2020;Alves et al, 2021;Banerjee et al, 2021;Gunther et al, 2021;Guo et al, 2021;Gupta et al, 2021;Hamdy et al, 2021;Pathak et al, 2021;Yang et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

A Computer-Aided Approach for the Discovery of D-Peptides as Inhibitors of SARS-CoV-2 Main Protease

González

Eberle

Willbold

et al. 2022

Front. Mol. Biosci.

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The SARS-CoV-2 main protease, also known as 3-chymotrypsin-like protease (3CLpro), is a cysteine protease responsible for the cleavage of viral polyproteins pp1a and pp1ab, at least, at eleven conserved sites, which leads to the formation of mature nonstructural proteins essential for the replication of the virus. Due to its essential role, numerous studies have been conducted so far, which have confirmed 3CLpro as an attractive drug target to combat Covid-19 and have reported a vast number of inhibitors and their co-crystal structures. Despite all the ongoing efforts, D-peptides, which possess key advantages over L-peptides as therapeutic agents, have not been explored as potential drug candidates against 3CLpro. The current work fills this gap by reporting an in silico approach for the discovery of D-peptides capable of inhibiting 3CLpro that involves structure-based virtual screening (SBVS) of an in-house library of D-tripeptides and D-tetrapeptides into the protease active site and subsequent rescoring steps, including Molecular Mechanics Generalized-Born Surface Area (MM-GBSA) free energy calculations and molecular dynamics (MD) simulations. In vitro enzymatic assays conducted for the four top-scoring D-tetrapeptides at 20 μM showed that all of them caused 55–85% inhibition of 3CLpro activity, thus highlighting the suitability of the devised approach. Overall, our results present a promising computational strategy to identify D-peptides capable of inhibiting 3CLpro, with broader application in problems involving protein inhibition.

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“…Recent studies in anti-COVID-19 drug discovery have highlighted the potential of polyphenolic compounds through in silicoguided investigations against protein targets in SARS-CoV-2 involved in infective mechanisms, i.e., inhibition of spike (S) protein, angiotensin-converting enzyme 2 (ACE-2) receptor, papain-like protease (PLpro), 3chymotrypsin-like cysteine protease (3CLpro), and RNAdependent-RNA-polymerase (RdRp) [10][11][12][13]. In addition, computational studies describing the potential of other classes of natural products as SARS-CoV-2 3CLpro, PLpro, and RdRp protein inhibitors have been reported [5,[14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Anti-HIV reverse transcriptase plant polyphenolic natural products with in silico inhibitory properties on seven non-structural proteins vital in SARS-CoV-2 pathogenesis

Leon

Manzano

Pilapil

et al. 2021

Journal of Genetic Engineering and Biotechnology

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Background Accessing COVID-19 vaccines is a challenge despite successful clinical trials. This burdens the COVID-19 treatment gap, thereby requiring accelerated discovery of anti-SARS-CoV-2 agents. This study explored the potential of anti-HIV reverse transcriptase (RT) phytochemicals as inhibitors of SARS-CoV-2 non-structural proteins (nsps) by targeting in silico key sites in the structures of SARS-CoV-2 nsps. One hundred four anti-HIV phytochemicals were subjected to molecular docking with nsp3, 5, 10, 12, 13, 15, and 16. Top compounds in complex with the nsps were investigated further through molecular dynamics. The drug-likeness and ADME (absorption, distribution, metabolism, and excretion) properties of the top compounds were also predicted using SwissADME. Their toxicity was likewise determined using OSIRIS Property Explorer. Results Among the top-scoring compounds, the polyphenolic functionalized natural products comprised of biflavones 1, 4, 11, 13, 14, 15; ellagitannin 9; and bisisoquinoline alkaloid 19 were multi-targeting and exhibited strongest binding affinities to at least two nsps (binding energy = − 7.7 to − 10.8 kcal/mol). The top ligands were stable in complex with their target nsps as determined by molecular dynamics. Several top-binding compounds were computationally druggable, showed good gastrointestinal absorptive property, and were also predicted to be non-toxic. Conclusions Twenty anti-HIV RT phytochemicals showed multi-targeting inhibitory potential against SARS-CoV-2 non-structural proteins 3, 5, 10, 12, 13, 15, and 16. Our results highlight the importance of polyhydroxylated aromatic substructures for effective attachment in the binding/catalytic sites of nsps involved in post-translational mechanism pathways. As such with the nsps playing vital roles in viral pathogenesis, our findings provide inspiration for the design and discovery of novel anti-COVID-19 drug prototypes.

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Black tea bioactives as inhibitors of multiple targets of SARS-CoV-2 (3CLpro, PLpro and RdRp): a virtual screening and molecular dynamic simulation study

Cited by 23 publications

References 60 publications

Targeting autophagy with natural products to prevent SARS-CoV-2 infection

Targeting autophagy with natural products to prevent SARS-CoV-2 infection

A Computer-Aided Approach for the Discovery of D-Peptides as Inhibitors of SARS-CoV-2 Main Protease

Anti-HIV reverse transcriptase plant polyphenolic natural products with in silico inhibitory properties on seven non-structural proteins vital in SARS-CoV-2 pathogenesis

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