Rutin and flavone analogs as prospective SARS-CoV-2 main protease inhibitors: In silico drug discovery study

Ibrahim, Mahmoud A. A.; Mohamed, Eslam A.R.; Abdelrahman, Alaa H. M.; Allemailem, Khaled S.; Moustafa, Mahmoud; Shawky, Ahmed M.; Mahzari, Ali; Hakami, Abdulrahim R.; Abdeljawaad, Khlood A. A.; Atia, Mohamed A. M.

doi:10.1016/j.jmgm.2021.107904

Cited by 56 publications

(35 citation statements)

References 50 publications

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“… S.No. Compound a MM/GBSA binding energies (Kcal/mol) References 1 Lithospermic acid B −118.7 [49] 2 Ritonavir −107.6 [50] 3 AT1001 −106.3 [53] 4 GHRP-2 –106.0 [54] 5 Rutin −99.8 [51] 6 N3 −80.0 [55] 7 ChemDiv_D658-0159 −77.5 [56] 8 Amikacin −73.8 [52] 9 γ-glutamyl-S-allylcysteine −72.5 [57] 10 ZINC000003947429 −70.4 [58] 11 PubChem-129-716-607 −69.0 [59] 12 11b −65.6 [60] a Compound name has been kept same as reported in respective literature. …”

Section: Resultsmentioning

confidence: 99%

Targeting SARS-CoV-2 main protease by teicoplanin: A mechanistic insight by docking, MM/GBSA and molecular dynamics simulation

Azam

Eid

Almutairi

2021

Journal of Molecular Structure

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First emerged in late December 2019, the outbreak of novel severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) pandemic has instigated public-health emergency around the globe. Till date there is no specific therapeutic agent for this disease and hence, the world is craving to identify potential antiviral agents against SARS-CoV-2. The main protease (M Pro ) is considered as an attractive drug target for rational drug design against SARS-CoV-2 as it is known to play a crucial role in the viral replication and transcription. Teicoplanin is a glycopeptide class of antibiotic which is regularly used for treating Gram-positive bacterial infections, has shown potential therapeutic efficacy against SARS-CoV-2 in vitro . Therefore, in this study, a mechanistic insight of intermolecular interactions between teicoplanin and SARS-CoV-2 main protease (M Pro ) has been scrutinized by molecular docking. Both monomeric and dimeric forms of M Pro was used in docking involving blind as well as defined binding site based on the known inhibitor. Binding energies of teicoplanin-M Pro complex were estimated by Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) computations from docking and simulated trajectories. The dynamic and thermodynamics constraints of docked drug in complex with target proteins under specific physiological conditions was ascertained by all-atom molecular dynamics simulation of 100 ns trajectory. Root mean square deviation and fluctuation of carbon α chain justified the stability of the bound complex in biological environments. The outcomes of current study are supposed to be fruitful in rational design of antiviral drugs against SARS-CoV-2.

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Section: Resultsmentioning

confidence: 99%

Targeting SARS-CoV-2 main protease by teicoplanin: A mechanistic insight by docking, MM/GBSA and molecular dynamics simulation

Azam

Eid

Almutairi

2021

Journal of Molecular Structure

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“…Among the explored natural products, salvanolic acid and curcumin accentuated appreciable MM-GBSA binding energies against M pro over 40 ns MD course with values of −44.8 and −34.2 kcal/mol, respectively [ 11 ]. Notably, rutin, a flavonol glycoside molecule, exhibited a debilitated binding affinity against M pro (Δ G binding = −28.4 kcal/mol over 150 ns MD simulation) [ 7 ]. Two flavone nominees dubbed as PubChem-129-716-607 and PubChem-885-071-27 showed considerable binding affinities against M pro , over 150 ns MD course, with Δ G binding values of −69.0 and −68.1 kcal/mol, respectively [ 7 ].…”

Section: Resultsmentioning

confidence: 99%

“…Notably, rutin, a flavonol glycoside molecule, exhibited a debilitated binding affinity against M pro (Δ G binding = −28.4 kcal/mol over 150 ns MD simulation) [ 7 ]. Two flavone nominees dubbed as PubChem-129-716-607 and PubChem-885-071-27 showed considerable binding affinities against M pro , over 150 ns MD course, with Δ G binding values of −69.0 and −68.1 kcal/mol, respectively [ 7 ]. Erylosides B, a terpene marine natural product, demonstrated preferential MM-GBSA binding energy with M pro over 100 ns MD simulation (calc.…”

Section: Resultsmentioning

confidence: 99%

“…Drug repurposing can be achieved by conducting systematic drug-drug target interaction and drug-drug interaction analyses [ 6 ]. Another approach is to examine a class or source of natural products with established biological activity; indeed, several in silico studies have been developed to screen for SARS-CoV-2 inhibitors as prospective anti-COVID-19 drug candidates [ 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Natural products play a pivotal role in designing novel and efficient treatments to conquer the current COVID-19 epidemic.…”

Section: Introductionmentioning

confidence: 99%

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Blue Biotechnology: Computational Screening of Sarcophyton Cembranoid Diterpenes for SARS-CoV-2 Main Protease Inhibition

et al. 2021

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The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (Mpro) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for potential antiviral drugs that target Mpro, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 Mpro inhibitors. Over 360 metabolites from the genus were screened using molecular docking calculations. Promising diterpenes were further characterized by molecular dynamics (MD) simulations based on molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. According to in silico calculations, five cembranoid diterpenes manifested adequate binding affinities as Mpro inhibitors with ΔGbinding < −33.0 kcal/mol. Binding energy and structural analyses of the most potent Sarcophyton inhibitor, bislatumlide A (340), was compared to darunavir, an HIV protease inhibitor that has been recently subjected to clinical-trial as an anti-COVID-19 drug. In silico analysis indicates that 340 has a higher binding affinity against Mpro than darunavir with ΔGbinding values of −43.8 and −34.8 kcal/mol, respectively throughout 100 ns MD simulations. Drug-likeness calculations revealed robust bioavailability and protein-protein interactions were identified for 340; biochemical signaling genes included ACE, MAPK14 and ESR1 as identified based on a STRING database. Pathway enrichment analysis combined with reactome mining revealed that 340 has the capability to re-modulate the p38 MAPK pathway hijacked by SARS-CoV-2 and antagonize injurious effects. These findings justify further in vivo and in vitro testing of 340 as an antiviral agent against SARS-CoV-2.

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“…Analysis of the core of the substrate-binding pocket revealed multiple interactions (such as hydrogen bonding with Leu141/Gly143 and Ser144/His163, π–π interactions with Cys145 and His4, and hydrophobic interactions with Met49 and His41), which effectively blocked SARS-CoV-2 replication via noncovalent incorporation [ 68 ]. The relevant studies [ 70 , 71 , 72 ] provided direct data for a better understanding of the molecular mechanisms of Chinese herbal medicine by studying its active ingredients.…”

Section: Natural Products As Monotherapy For the Treatment Of Sars-cov-2mentioning

confidence: 99%

Natural Products, Alone or in Combination with FDA-Approved Drugs, to Treat COVID-19 and Lung Cancer

Yang

Wang

2021

Biomedicines

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As a public health emergency of international concern, the highly contagious coronavirus disease 2019 (COVID-19) pandemic has been identified as a severe threat to the lives of billions of individuals. Lung cancer, a malignant tumor with the highest mortality rate, has brought significant challenges to both human health and economic development. Natural products may play a pivotal role in treating lung diseases. We reviewed published studies relating to natural products, used alone or in combination with US Food and Drug Administration-approved drugs, active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and lung cancer from 1 January 2020 to 31 May 2021. A wide range of natural products can be considered promising anti-COVID-19 or anti-lung cancer agents have gained widespread attention, including natural products as monotherapy for the treatment of SARS-CoV-2 (ginkgolic acid, shiraiachrome A, resveratrol, and baicalein) or lung cancer (daurisoline, graveospene A, deguelin, and erianin) or in combination with FDA-approved anti-SARS-CoV-2 agents (cepharanthine plus nelfinavir, linoleic acid plus remdesivir) and anti-lung cancer agents (curcumin and cisplatin, celastrol and gefitinib). Natural products have demonstrated potential value and with the assistance of nanotechnology, combination drug therapies, and the codrug strategy, this “natural remedy” could serve as a starting point for further drug development in treating these lung diseases.

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Rutin and flavone analogs as prospective SARS-CoV-2 main protease inhibitors: In silico drug discovery study

Cited by 56 publications

References 50 publications

Targeting SARS-CoV-2 main protease by teicoplanin: A mechanistic insight by docking, MM/GBSA and molecular dynamics simulation

Targeting SARS-CoV-2 main protease by teicoplanin: A mechanistic insight by docking, MM/GBSA and molecular dynamics simulation

Blue Biotechnology: Computational Screening of Sarcophyton Cembranoid Diterpenes for SARS-CoV-2 Main Protease Inhibition

Natural Products, Alone or in Combination with FDA-Approved Drugs, to Treat COVID-19 and Lung Cancer

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