Virtual Screening of Phytochemicals by Targeting HR1 Domain of SARS-CoV-2 S Protein: Molecular Docking, Molecular Dynamics Simulations, and DFT Studies.

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  • Additional Information
    • Source:
      Publisher: Hindawi Pub. Co Country of Publication: United States NLM ID: 101600173 Publication Model: eCollection Cited Medium: Internet ISSN: 2314-6141 (Electronic) NLM ISO Abbreviation: Biomed Res Int Subsets: MEDLINE
    • Publication Information:
      Original Publication: New York, NY : Hindawi Pub. Co.
    • Subject Terms:
      COVID-19 Drug Treatment*; Antiviral Agents/*pharmacology ; Phytochemicals/*pharmacology ; Spike Glycoprotein, Coronavirus/*antagonists & inhibitors; Antiviral Agents/chemistry ; Binding Sites ; COVID-19/virology ; Density Functional Theory ; Drug Discovery ; Humans ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Phytochemicals/chemistry ; Protein Domains ; SARS-CoV-2/drug effects ; SARS-CoV-2/isolation & purification
    • Abstract:
      The recent COVID-19 pandemic has impacted nearly the whole world due to its high morbidity and mortality rate. Thus, scientists around the globe are working to find potent drugs and designing an effective vaccine against COVID-19. Phytochemicals from medicinal plants are known to have a long history for the treatment of various pathogens and infections; thus, keeping this in mind, this study was performed to explore the potential of different phytochemicals as candidate inhibitors of the HR1 domain in SARS-CoV-2 spike protein by using computer-aided drug discovery methods. Initially, the pharmacological assessment was performed to study the drug-likeness properties of the phytochemicals for their safe human administration. Suitable compounds were subjected to molecular docking to screen strongly binding phytochemicals with HR1 while the stability of ligand binding was analyzed using molecular dynamics simulations. Quantum computation-based density functional theory (DFT) analysis was constituted to analyze the reactivity of these compounds with the receptor. Through analysis, 108 phytochemicals passed the pharmacological assessment and upon docking of these 108 phytochemicals, 36 were screened passing a threshold of -8.5 kcal/mol. After analyzing stability and reactivity, 5 phytochemicals, i.e., SilybinC, Isopomiferin, Lycopene, SilydianinB, and Silydianin are identified as novel and potent candidates for the inhibition of HR1 domain in SARS-CoV-2 spike protein. Based on these results, it is concluded that these compounds can play an important role in the design and development of a drug against COVID-19, after an exhaustive in vitro and in vivo examination of these compounds, in future.
      Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper.
      (Copyright © 2021 Arshia Majeed et al.)
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    • Accession Number:
      0 (Antiviral Agents)
      0 (Phytochemicals)
      0 (Spike Glycoprotein, Coronavirus)
      0 (spike protein, SARS-CoV-2)
    • Publication Date:
      Date Created: 20210607 Date Completed: 20210617 Latest Revision: 20221207
    • Publication Date:
      20240104
    • Accession Number:
      PMC8139335
    • Accession Number:
      10.1155/2021/6661191
    • Accession Number:
      34095308