Identifying the Most Potent Dual-Targeting Compound(s) against 3CLprotease and NSP15exonuclease of SARS-CoV-2 from Nigella sativa: Virtual Screening via Physicochemical Properties, Docking and Dynamic Simulation Analysis
et al., Processes, doi:10.3390/pr9101814, Oct 2021
13th treatment shown to reduce risk in
January 2021, now with p = 0.00016 from 14 studies.
No treatment is 100% effective. Protocols
combine treatments.
6,300+ studies for
210+ treatments. c19early.org
|
In silico study predicting that nigella sativa component dithymoquinone has good affinity and stability against SARS-CoV-2 3CLpro and NSP15, suggesting potential benefits for COVID-19 treatment.
22 preclinical studies support the efficacy of nigella sativa for COVID-19:
1.
Rahman et al., In silico Screening of Potential Drug Candidate against Chain a of Coronavirus Binding Protein from Major Nigella Bioactive Compounds, Asian Journal of Advanced Research and Reports, doi:10.9734/ajarr/2024/v18i7697.
2.
Zafar Nayak Snehasis, S., Molecular Docking to Discover Potential Bio-Extract Substitutes for Hydroxychloroquine against COVID-19 and Malaria, International Journal of Science and Research (IJSR), doi:10.21275/SR24323192940.
3.
Alkafaas et al., A study on the effect of natural products against the transmission of B.1.1.529 Omicron, Virology Journal, doi:10.1186/s12985-023-02160-6.
4.
Ali et al., Computational Prediction of Nigella sativa Compounds as Potential Drug Agents for Targeting Spike Protein of SARS-CoV-2, Pakistan BioMedical Journal, doi:10.54393/pbmj.v6i3.853.
5.
Miraz et al., Nigelladine A among Selected Compounds from Nigella sativa Exhibits Propitious Interaction with Omicron Variant of SARS-CoV-2: An In Silico Study, International Journal of Clinical Practice, doi:10.1155/2023/9917306.
6.
Sherwani et al., Pharmacological Profile of Nigella sativa Seeds in Combating COVID-19 through In-Vitro and Molecular Docking Studies, Processes, doi:10.3390/pr10071346.
7.
Khan et al., Inhibitory effect of thymoquinone from Nigella sativa against SARS-CoV-2 main protease. An in-silico study, Brazilian Journal of Biology, doi:10.1590/1519-6984.25066.
8.
Esharkawy et al., In vitro Potential Antiviral SARS-CoV-19- Activity of Natural Product Thymohydroquinone and Dithymoquinone from Nigela sativia, Bioorganic Chemistry, doi:10.1016/j.bioorg.2021.105587.
9.
Banerjee et al., Nigellidine (Nigella sativa, black-cumin seed) docking to SARS CoV-2 nsp3 and host inflammatory proteins may inhibit viral replication/transcription, Natural Product Research, doi:10.1080/14786419.2021.2018430.
10.
Rizvi et al., Identifying the Most Potent Dual-Targeting Compound(s) against 3CLprotease and NSP15exonuclease of SARS-CoV-2 from Nigella sativa: Virtual Screening via Physicochemical Properties, Docking and Dynamic Simulation Analysis, Processes, doi:10.3390/pr9101814.
11.
Mir et al., Identification of SARS-CoV-2 RNA-dependent RNA polymerase inhibitors from the major phytochemicals of Nigella sativa: An in silico approach, Saudi Journal of Biological Sciences, doi:10.1016/j.sjbs.2021.09.002.
12.
Hardianto et al., Exploring the Potency of Nigella sativa Seed in Inhibiting SARS-CoV-2 Main Protease Using Molecular Docking and Molecular Dynamics Simulations, Indonesian Journal of Chemistry, doi:10.22146/ijc.65951.
13.
Maiti et al., Active-site Molecular docking of Nigellidine to nucleocapsid/Nsp2/Nsp3/MPro of COVID-19 and to human IL1R and TNFR1/2 may stop viral-growth/cytokine-flood, and the drug source Nigella sativa (black cumin) seeds show potent antioxidant role in experimental rats, Research Square, doi:10.21203/rs.3.rs-26464/v1.
14.
Duru et al., In silico identification of compounds from Nigella sativa seed oil as potential inhibitors of SARS-CoV-2 targets, Bulletin of the National Research Centre, doi:10.1186/s42269-021-00517-x.
15.
Bouchentouf et al., Identification of Compounds from Nigella Sativa as New Potential Inhibitors of 2019 Novel Coronasvirus (Covid-19): Molecular Docking Study, ChemRxiv, doi:10.26434/chemrxiv.12055716.v1.
16.
Ali (B) et al., In vitro inhibitory effect of Nigella sativa L. extracts on SARS-COV-2 spike protein-ACE2 interaction, Current Therapeutic Research, doi:10.1016/j.curtheres.2024.100759.
17.
Bostancıklıoğlu et al., Nigella sativa, Anthemis hyaline and Citrus sinensis extracts reduce SARS-CoV-2 replication by fluctuating Rho GTPase, PI3K-AKT, and MAPK/ERK pathways in HeLa-CEACAM1a cells, Gene, doi:10.1016/j.gene.2024.148366.
Rizvi et al., 13 Oct 2021, peer-reviewed, 10 authors.
In silico studies are an important part of preclinical research, however results may be very different in vivo.
Identifying the Most Potent Dual-Targeting Compound(s) against 3CLprotease and NSP15exonuclease of SARS-CoV-2 from Nigella sativa: Virtual Screening via Physicochemical Properties, Docking and Dynamic Simulation Analysis
Processes, doi:10.3390/pr9101814
Background: The outbreak of the coronavirus (SARS-CoV-2) has drastically affected the human population and caused enormous economic deprivation. It belongs to the β-coronavirus family and causes various problems such as acute respiratory distress syndrome and has resulted in a global pandemic. Though various medications have been under trial for combating COVID-19, specific medicine for treating COVID-19 is unavailable. Thus, the current situation urgently requires effective treatment modalities. Nigella sativa, a natural herb with reported antiviral activity and various pharmacological properties, has been selected in the present study to identify a therapeutic possibility for treating COVID-19. Methods: The present work aimed to virtually screen the bioactive compounds of N. sativa based on the physicochemical properties and docking approach against two SARS-CoV-2 enzymes responsible for crucial functions: 3CLpro (Main protease) and NSP15 (Nonstructural protein 15 or exonuclease). However, simulation trajectory analyses for 100 ns were accomplished by using the YASARA STRUCTURE tool based on the AMBER14 force field with 400 snapshots every 250 ps. RMSD and RMSF plots were successfully obtained for each target. Results: The results of molecular docking have shown higher binding energy of dithymoquinone (DTQ), a compound of N. sativa against 3CLpro and Nsp15, i.e., −8.56 kcal/mol and −8.31 kcal/mol, respectively. Further, the dynamic simulation has shown good stability of DTQ against both the targeted enzymes. In addition, physicochemical evaluation and toxicity assessment also revealed that DTQ obeyed the Lipinski rule and did not have any toxic side effects. Importantly, DTQ was much better in every aspect among the 13 N. sativa compounds and 2 control compounds tested. Conclusions: The results predicted that DTQ is a potent therapeutic molecule that could dual-target both 3CLpro and NSP15 for anti-COVID therapy.
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