In silico study of natural compounds from sesame against COVID-19 by targeting Mpro, PLpro and RdRp

Allam, Ahmed E.; Amen, Yhiya; Ashour, Ahmed; Assaf, Hamdy K.; Hassan, Heba A.; Abdel-Rahman, Islam M.; Sayed, Ahmed M.; Shimizu, Kuniyoshi

doi:10.1039/d1ra03937g

Cited by 34 publications

(38 citation statements)

References 51 publications

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“…Other studies also indicated that the sesamin compound might interact with amino acid residues Ser144, Cys145, Gln189, and Gln192 and showed significant interactions with effective residues His41, Met49, and Met165 of the M pro of COVID-19 (Pandey and Verma, 2020). In a follow-up study, Allam et al (2021) explored the sesamin and sesamolin compounds along with other natural compounds against M pro , PL pro , and RdRp proteins. Sesamin was found to be interacted with M pro with three residues including Gln189, Thr190, and His41, while the sesamolin molecule was reported to interact with two amino acid residues, namely, Gln189 and Thr190.…”

Section: Compoundmentioning

confidence: 99%

“…In a recent study, Pandey and Verma (2020) also studied the potential of sesamin and four other dietary components (galangin, ellagic acid, capsaicin, and epicatechin) as structural inhibitors of SARS-CoV-2 M pro using the molecular docking approach. In a very recent study, Allam et al (2021) reported seven sesame-derived natural compounds (sesamin, sesamolin, pinoresinol, hydroxymatairesinol, spicatolignan, ferulic acid, and vanillic acid) as potential inhibitors against three proteins of SARS-CoV-2 including M pro , papain-like protease (PL pro ), and the RNA-dependent RNA polymerase (RdRp) using the molecular docking analysis followed by MD simulations on 50 ns for representative complexes. However, there is no significant evidence of docking results evaluation available for MD simulations on high nanosecond scale (up to 200 ns) to understand the inhibitory mechanism of all sesame-derived compounds against the SARS-CoV-2 proteins.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition Potencies of Phytochemicals Derived from Sesame Against SARS-CoV-2 Main Protease: A Molecular Docking and Simulation Study

et al. 2021

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The ongoing COVID-19 pandemic, caused by SARS-CoV-2, has now spread across the nations with high mortality rates and multifaceted impact on human life. The proper treatment methods to overcome this contagious disease are still limited. The main protease enzyme (Mpro, also called 3CLpro) is essential for viral replication and has been considered as one of the potent drug targets for treating COVID-19. In this study, virtual screening was performed to find out the molecular interactions between 36 natural compounds derived from sesame and the Mpro of COVID-19. Four natural metabolites, namely, sesamin, sesaminol, sesamolin, and sesamolinol have been ranked as the top interacting molecules to Mpro based on the affinity of molecular docking. Moreover, stability of these four sesame-specific natural compounds has also been evaluated using molecular dynamics (MD) simulations for 200 nanoseconds. The molecular dynamics simulations and free energy calculations revealed that these compounds have stable and favorable energies, causing strong binding with Mpro. These screened natural metabolites also meet the essential conditions for drug likeness such as absorption, distribution, metabolism, and excretion (ADME) properties as well as Lipinski’s rule of five. Our finding suggests that these screened natural compounds may be evolved as promising therapeutics against COVID-19.

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Section: Compoundmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition Potencies of Phytochemicals Derived from Sesame Against SARS-CoV-2 Main Protease: A Molecular Docking and Simulation Study

et al. 2021

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“…The production part was carried out for 100 ns with the time step of 2 fs. Pymol and VMD 1.9.1 ( 36 ) were used to visualize the trajectory. Lastly, data analyses were performed for each complex and free PLpro by using root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), the radius of gyration (Rg), and solvent-accessible surface area (SASA).…”

Section: Docking Methodologymentioning

confidence: 99%

Investigating Fungi-Derived Bioactive Molecules as Inhibitor of the SARS Coronavirus Papain Like Protease: Computational Based Study

et al. 2021

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Due to the rapid growth of the COVID-19 pandemic and its outcomes, developing a remedy to fight the predicament is critical. So far, it has infected more than 214,468,601 million people and caused the death of 4,470,969 million people according to the August 27, 2021, World Health Organization's (WHO) report. Several studies have been published on both computational and wet-lab approaches to develop antivirals for COVID-19, although there has been no success yet. However, the wet-lab approach is laborious, expensive, and time-consuming, and computational techniques have screened the activity of bioactive compounds from different sources with less effort and cost. For this investigation, we screened the binding affinity of fungi-derived bioactive molecules toward the SARS coronavirus papain-like protease (PLpro) by using computational approaches. Studies showed that protease inhibitors can be very effective in controlling virus-induced infections. Additionally, fungi represent a vast source of bioactive molecules, which could be potentially used for antiviral therapy. Fifty fungi-derived bioactive compounds were investigated concerning SARS-CoV-2 PLpro by using Auto Dock 4.2.1, Gromacs 2018. 2, ADMET, Swiss-ADME, FAF-Drugs 4.023, pKCSM, and UCLA-DOE server. From the list of the screened bioactive compounds, Dihydroaltersolanol C, Anthraquinone, Nigbeauvin A, and Catechin were selected with the Auto-Dock results of −8.68, −7.52, −10.46, and −10.58 Kcal/mol, respectively, based on their binding affinity compared to the reference drug. We presented the drug likeliness, toxicity, carcinogenicity, and mutagenicity of all compounds using ADMET analysis. They interacted with the amino acid residues, Gly163, Trp106, Ser111, Asp164, and Cys270, through hydrogen bonds. The root-mean-square deviation (RMSD), root-mean-square fluctuations (RMSF), solvent-accessible surface area (SASA), and radius of gyration (Rg) values revealed a stable interaction. From the overall analyses, we can conclude that Dihydroaltersolanol C, Anthraquinone, Nigbeauvin A, and Catechin are classified as promising candidates for PLpro, thus potentially useful in developing a medicine for COVID-19.

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“…RdRp has proven to be a good antiviral target for coronaviruses, and several intriguing compounds have antiviral effects by targeting RdRp-for example, theaflavin [33]. Moreover, sesamin, sesamolin, pinoresinol, hydroxymatairesinol, spicatolignan, ferulic acid, and vanillic acid were tested in silico against three major proteins of SARS-CoV-2, including, 3CLpro, PLpro and RdRp [195]. Moreover, a virus replication enzyme, helicase or Nsp13, is involved in the unwinding of viral RNA.…”

Section: The Therapeutic Targets Against Coronavirusmentioning

confidence: 99%

Coronavirus Infection-Associated Cell Death Signaling and Potential Therapeutic Targets

2021

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COVID-19 is the name of the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that occurred in 2019. The virus–host-specific interactions, molecular targets on host cell deaths, and the involved signaling are crucial issues, which become potential targets for treatment. Spike protein, angiotensin-converting enzyme 2 (ACE2), cathepsin L-cysteine peptidase, transmembrane protease serine 2 (TMPRSS2), nonstructural protein 1 (Nsp1), open reading frame 7a (ORF7a), viral main protease (3C-like protease (3CLpro) or Mpro), RNA dependent RNA polymerase (RdRp) (Nsp12), non-structural protein 13 (Nsp13) helicase, and papain-like proteinase (PLpro) are molecules associated with SARS-CoV infection and propagation. SARS-CoV-2 can induce host cell death via five kinds of regulated cell death, i.e., apoptosis, necroptosis, pyroptosis, autophagy, and PANoptosis. The mechanisms of these cell deaths are well established and can be disrupted by synthetic small molecules or natural products. There are a variety of compounds proven to play roles in the cell death inhibition, such as pan-caspase inhibitor (z-VAD-fmk) for apoptosis, necrostatin-1 for necroptosis, MCC950, a potent and specific inhibitor of the NLRP3 inflammasome in pyroptosis, and chloroquine/hydroxychloroquine, which can mitigate the corresponding cell death pathways. However, NF-κB signaling is another critical anti-apoptotic or survival route mediated by SARS-CoV-2. Such signaling promotes viral survival, proliferation, and inflammation by inducing the expression of apoptosis inhibitors such as Bcl-2 and XIAP, as well as cytokines, e.g., TNF. As a result, tiny natural compounds functioning as proteasome inhibitors such as celastrol and curcumin can be used to modify NF-κB signaling, providing a responsible method for treating SARS-CoV-2-infected patients. The natural constituents that aid in inhibiting viral infection, progression, and amplification of coronaviruses are also emphasized, which are in the groups of alkaloids, flavonoids, terpenoids, diarylheptanoids, and anthraquinones. Natural constituents derived from medicinal herbs have anti-inflammatory and antiviral properties, as well as inhibitory effects, on the viral life cycle, including viral entry, replication, assembly, and release of COVID-19 virions. The phytochemicals contain a high potential for COVID-19 treatment. As a result, SARS-CoV-2-infected cell death processes and signaling might be of high efficacy for therapeutic targeting effects and yielding encouraging outcomes.

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In silico study of natural compounds from sesame against COVID-19 by targeting M^pro, PL^pro and RdRp

Abstract: Natural products and traditional medicine products with known safety profiles are a promising source for the discovery of new drug leads.

Cited by 34 publications

References 51 publications

Inhibition Potencies of Phytochemicals Derived from Sesame Against SARS-CoV-2 Main Protease: A Molecular Docking and Simulation Study

Inhibition Potencies of Phytochemicals Derived from Sesame Against SARS-CoV-2 Main Protease: A Molecular Docking and Simulation Study

Investigating Fungi-Derived Bioactive Molecules as Inhibitor of the SARS Coronavirus Papain Like Protease: Computational Based Study

Coronavirus Infection-Associated Cell Death Signaling and Potential Therapeutic Targets

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