Anti-dengue infectivity evaluation of bioflavonoid from <i>Azadirachta indica</i> by dengue virus serine protease inhibition

Dwivedi, Vivek Dhar; Bharadwaj, Shiv; Afroz, Sumbul; Khan, Nooruddin; Ansari, Mairaj Ahmed; Yadava, Umesh; Tripathi, Ramesh C.; Tripathi, I. P.; Mishra, Sarad Kumar; Kang, Sang Gu

doi:10.1080/07391102.2020.1734485

Cited by 56 publications

(37 citation statements)

References 55 publications

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“…The virtual screening technique is used in the identification of small molecules from large compound databases, which hold considerable affinity with the active pocket of receptor [ 48–50 ]. Screening of natural compound libraries is of great interest because of high chemical diversity, biochemical specificity, and other molecular descriptor properties that make them favorable as lead ligands in drug discovery [ 51 , 52 ]. Herein, virtual screening of SARS-CoV-2 M pro against NP-lib database at MTiOpenScreen webserver results in collection of 654 compounds with docking score between −10 and −4 kcal/mol ( Table S1 ).…”

Section: Resultsmentioning

confidence: 99%

Exploration of natural compounds with anti-SARS-CoV-2 activityviainhibition of SARS-CoV-2 Mpro

Bharadwaj

Dubey

Yadava

et al. 2021

Briefings in Bioinformatics

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148

114

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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a dreaded pandemic in lack of specific therapeutic agent. SARS-CoV-2 Mpro, an essential factor in viral pathogenesis, is recognized as a prospective therapeutic target in drug discovery against SARS-CoV-2. To tackle this pandemic, Food and Drug Administration-approved drugs are being screened against SARS-CoV-2 Mpro via in silico and in vitro methods to detect the best conceivable drug candidates. However, identification of natural compounds with anti-SARS-CoV-2 Mpro potential have been recommended as rapid and effective alternative for anti-SARS-CoV-2 therapeutic development. Thereof, a total of 653 natural compounds were identified against SARS-CoV-2 Mpro from NP-lib database at MTi-OpenScreen webserver using virtual screening approach. Subsequently, top four potential compounds, i.e. 2,3-Dihydroamentoflavone (ZINC000043552589), Podocarpusflavon-B (ZINC000003594862), Rutin (ZINC000003947429) and Quercimeritrin 6”-O-L-arabinopyranoside (ZINC000070691536), and co-crystallized N3 inhibitor as reference ligand were considered for stringent molecular docking after geometry optimization by DFT method. Each compound exhibited substantial docking energy >−12 kcal/mol and molecular contacts with essential residues, including catalytic dyad (His41 and Cys145) and substrate binding residues, in the active pocket of SARS-CoV-2 Mpro against N3 inhibitor. The screened compounds were further scrutinized via absorption, distribution, metabolism, and excretion - toxicity (ADMET), quantum chemical calculations, combinatorial molecular simulations and hybrid QM/MM approaches. Convincingly, collected results support the potent compounds for druglikeness and strong binding affinity with the catalytic pocket of SARS-CoV-2 Mpro. Hence, selected compounds are advocated as potential inhibitors of SARS-CoV-2 Mpro and can be utilized in drug development against SARS-CoV-2 infection.

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Section: Resultsmentioning

confidence: 99%

Exploration of natural compounds with anti-SARS-CoV-2 activityviainhibition of SARS-CoV-2 Mpro

Bharadwaj

Dubey

Yadava

et al. 2021

Briefings in Bioinformatics

Self Cite

148

114

View full text Add to dashboard Cite

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“…Finally, MD simulation was performed for each selected docked complex under similar conditions for 100 ns interval. Subsequently, MD simulation trajectory for each system was investigated using simulation interaction diagram tool of the Desmond version 5.6 module in Schrödinger-Maestro version 11.8 package (Bharadwaj, Rao, et al., 2020 ; Dwivedi et al., 2020 ).…”

Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 M^proinhibitors: identification of anti-SARS-CoV-2 M^procompounds from FDA approved drugs

Bharadwaj

Azhar

Kamal

et al. 2020

Journal of Biomolecular Structure and Dynamics

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Recent outbreak of COVID-19 pandemic caused by severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) has raised serious global concern for public health. The viral main 3-chymotrypsin-like cysteine protease (M pro ), known to control coronavirus replication and essential for viral life cycle, has been established as an essential drug discovery target for SARS-CoV-2. Herein, we employed computationally screening of Druglib database containing FDA approved drugs against active pocket of SARS-CoV-2 M pro using MTiopen screen web server, yields a total of 1051 FDA approved drugs with docking energy >−7 kcal/mol. The top 10 screened potential compounds against SARS-CoV-2 M pro were then studied by re-docking, binding affinity, intermolecular interaction, and complex stability via 100 ns all atoms molecular dynamics (MD) simulation followed by post-simulation analysis, including end point binding free energy, essential dynamics, and residual correlation analysis against native crystal structure ligand N3 inhibitor. Based on comparative molecular simulation and interaction profiling of the screened drugs with SARS-CoV-2 M pro revealed R428 (−10.5 kcal/mol), Teniposide (−9.8 kcal/mol), VS-5584 (−9.4 kcal/mol), and Setileuton (−8.5 kcal/mol) with stronger stability and affinity than other drugs and N3 inhibitor; and hence, these drugs are advocated for further validation using in vitro enzyme inhibition and in vivo studies against SARS-CoV-2 infection. Communicated by Ramaswamy H. Sarma

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“…The leaves of neem (A. indica), a popular Indian plant, is traditionally boiled and consumed for treatment of fever (Burkill, 1935), with reported anti-inflammatory effects in animal studies (Schumacher et al, 2011). In vitro and in silico docking studies demonstrated that neem leaves extracts and its phytochemicals such as flavonoids and polysaccharides have direct antiviral effects against various viruses including dengue (Dwivedi et al, 2020) and Hepatitis C Virus (Ashfaq et al, 2016). Specific to SARS-CoV-2, molecular docking studies have demonstrated that the neem derived compounds nimbolin A, nimocin, and cycloartanols have the potential to bind to envelope (E) and membrane (M) glycoproteins of the SARS-CoV-2 and act as inhibitors (Borkotoky and Banerjee, 2020).…”

Section: Eurycoma Longifolia Jackmentioning

confidence: 99%

Medicinal Plants in COVID-19: Potential and Limitations

2021

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Currently, the search to identify treatments and vaccines for novel coronavirus disease (COVID-19) are ongoing. Desperation within the community, especially among the middle-and low-income groups acutely affected by the economic impact of forced lockdowns, has driven increased interest in exploring alternative choices of medicinal plant-based therapeutics. This is evident with the rise in unsubstantiated efficacy claims of these interventions circulating on social media. Based on enquiries received, our team of researchers was given the chance to produce evidence summaries evaluating the potential of complementary interventions in COVID-19 management. Here, we present and discuss the findings of four selected medicinal plants (Nigella sativa, Vernonia amygdalina, Azadirachta indica, Eurycoma longifolia), with reported antiviral, anti-inflammatory, and immunomodulatory effects that might be interesting for further investigation. Our findings showed that only A. indica reported positive antiviral evidence specific to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on preliminary in silico data while all four medicinal plants demonstrated differential anti-inflammatory or immunomodulatory effects. The definitive roles of these medicinal plants in cytokine storms and post-infection complications remains to be further investigated. Quality control and standardisation of medicinal plant-based products also needs to be emphasized. However, given the unprecedented challenges faced, ethnopharmacological research should be given a fair amount of consideration for contribution in this pandemic.

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Anti-dengue infectivity evaluation of bioflavonoid from Azadirachta indica by dengue virus serine protease inhibition

Cited by 56 publications

References 55 publications

Exploration of natural compounds with anti-SARS-CoV-2 activityviainhibition of SARS-CoV-2 Mpro

Exploration of natural compounds with anti-SARS-CoV-2 activityviainhibition of SARS-CoV-2 Mpro

SARS-CoV-2 M^proinhibitors: identification of anti-SARS-CoV-2 M^procompounds from FDA approved drugs

Medicinal Plants in COVID-19: Potential and Limitations

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Anti-dengue infectivity evaluation of bioflavonoid from Azadirachta indica by dengue virus serine protease inhibition

Cited by 56 publications

References 55 publications

Exploration of natural compounds with anti-SARS-CoV-2 activityviainhibition of SARS-CoV-2 Mpro

Exploration of natural compounds with anti-SARS-CoV-2 activityviainhibition of SARS-CoV-2 Mpro

SARS-CoV-2 Mproinhibitors: identification of anti-SARS-CoV-2 Mprocompounds from FDA approved drugs

Medicinal Plants in COVID-19: Potential and Limitations

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SARS-CoV-2 M^proinhibitors: identification of anti-SARS-CoV-2 M^procompounds from FDA approved drugs