Repurposing potential of Ayurvedic medicinal plants derived active principles against SARS-CoV-2 associated target proteins revealed by molecular docking, molecular dynamics and MM-PBSA studies
| العنوان: | Repurposing potential of Ayurvedic medicinal plants derived active principles against SARS-CoV-2 associated target proteins revealed by molecular docking, molecular dynamics and MM-PBSA studies |
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| المؤلفون: | Bhabesh Ch. Goswami, Sweta Singh, Keun Woo Lee, Sanghwa Yoon, Ihosvany Camps, Aishwarya Sekar, Akalesh K. Verma, Vikas Kumar |
| المصدر: | Biomedicine & Pharmacotherapy Biomedicine & Pharmacotherapy, Vol 137, Iss, Pp 111356-(2021) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, MD, molecular dynamics simulations, medicine.medical_treatment, NCBI, National Center for Biotechnology Information, Catechols, Pm, prediction score, MM-PBSA, molecular mechanics Poisson-Boltzmann surface area, Molecular Docking Simulation, AR, aryl, 0302 clinical medicine, Furin, HBD, hydrogen bond donor, COVID-19, coronavirus disease 2019, biology, Chemistry, General Medicine, Ligand (biochemistry), NI, negative ionizable, Biochemistry, 030220 oncology & carcinogenesis, Quercetin, Target protein, Pharmacophore, Fatty Alcohols, Curcumin, H, hydrophobic center, RM1-950, Antiviral Agents, Article, 03 medical and health sciences, Viral Proteins, RdRp, RNA dependent RNA polymerase, Viral entry, PDB, Protein Data Bank, medicine, Humans, Pharmacology, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, Protease, SARS-CoV-2, Drug Repositioning, COVID-19, ACE2, Angiotensin converting enzyme 2, Medicine, Ayurvedic, COVID-19 Drug Treatment, MDc, molecular docking, Coronavirus, Mpro, main protease, 030104 developmental biology, Docking (molecular), HBA, hydrogen bond acceptor, Main protease, RdRp, spike protein RBD, biology.protein, Therapeutics. Pharmacology, ACE-2, AS, applicability score |
| الوصف: | All the plants and their secondary metabolites used in the present study were obtained from Ayurveda, with historical roots in the Indian subcontinent. The selected secondary metabolites have been experimentally validated and reported as potent antiviral agents against genetically-close human viruses. The plants have also been used as a folk medicine to treat cold, cough, asthma, bronchitis, and severe acute respiratory syndrome in India and across the globe since time immemorial. The present study aimed to assess the repurposing possibility of potent antiviral compounds with SARS-CoV-2 target proteins and also with host-specific receptor and activator protease that facilitates the viral entry into the host body. Molecular docking (MDc) was performed to study molecular affinities of antiviral compounds with aforesaid target proteins. The top-scoring conformations identified through docking analysis were further validated by 100 ns molecular dynamic (MD) simulation run. The stability of the conformation was studied in detail by investigating the binding free energy using MM-PBSA method. Finally, the binding affinities of all the compounds were also compared with a reference ligand, remdesivir, against the target protein RdRp. Additionally, pharmacophore features, 3D structure alignment of potent compounds and Bayesian machine learning model were also used to support the MDc and MD simulation. Overall, the study emphasized that curcumin possesses a strong binding ability with host-specific receptors, furin and ACE2. In contrast, gingerol has shown strong interactions with spike protein, and RdRp and quercetin with main protease (Mpro) of SARS-CoV-2. In fact, all these target proteins play an essential role in mediating viral replication, and therefore, compounds targeting aforesaid target proteins are expected to block the viral replication and transcription. Overall, gingerol, curcumin and quercetin own multitarget binding ability that can be used alone or in combination to enhance therapeutic efficacy against COVID-19. The obtained results encourage further in vitro and in vivo investigations and also support the traditional use of antiviral plants preventively. |
| تدمد: | 1950-6007 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ec102c3500c7c74eb281c7061da56a53 https://pubmed.ncbi.nlm.nih.gov/33561649 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ec102c3500c7c74eb281c7061da56a53 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19506007 |
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