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Exploring the phytochemicals of Platycodon grandiflorus for TMPRSS2 inhibition in the search for SARS-CoV-2 entry inhibitors.
Gurung, Arun Bahadur; Ali, Mohammad Ajmal; Lee, Joongku; Aljowaie, Reem M; Almutairi, Saeedah M.
  • Gurung AB; Department of Basic Sciences and Social Sciences, North-Eastern Hill University, Shillong 793022, Meghalaya, India.
  • Ali MA; Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
  • Lee J; Department of Environment and Forest Resources, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea.
  • Aljowaie RM; Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
  • Almutairi SM; Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
J King Saud Univ Sci ; 34(6): 102155, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1882239
ABSTRACT
Platycodon grandiflorus (Jacq.) A. DC. (Campanulaceae) is commonly known as a balloon flower whose rhizomes have been widely utilized in traditional Chinese medicine (TCM) and in various Japanese prescriptions for the treatment of respiratory diseases, diabetes, and inflammatory disorders. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) global pandemic requires priming of the virus's spike (S) protein by cleavage of the S proteins by a multi-domain type II transmembrane serine protease, transmembrane protease serine 2 (TMPRSS2) to gain entry into the host cell. The current research aims at the screening of active phytocompounds of P. grandiflorus as potential inhibitors of cellular TMPRSS2 using molecular docking and molecular dynamics simulations approach. In silico toxicity analyses show that out of a total of 34 phytocompounds selected for the study, 12 compounds obey Lipinski's rule of five and have favourable pharmacokinetic properties. The top three lead molecules identified here were Apigenin, Luteolin and Ferulic acid which exhibited binding energies of -7.47 kcal/mol, -6.8 kcal/mol and -6.62 kcal/mol respectively with corresponding inhibition constants of 3.33 µM, 10.39 µM and 13.95 µM. The complexes between the lead molecules and the receptor were held by hydrogen bond interactions with key residues such as Gly383, Gly385, Glu389, Lys390, Asp435, Ser436, Ser441, Cys465 and Lys467, and hydrophobic interactions with surrounding residues. The stability of the protein-ligand complexes was evaluated during 100 ns molecular dynamics (MD) simulation by analysing key geometric properties such as RMSD, RMSF, radius of gyration, total solvent accessible surface area and the number of hydrogen bonds. The binding free energies analysis using MD simulations revealed that the compounds and TMPRSS2 have favourable thermodynamic interactions, which are primarily driven by van der Waals forces. As a result, the selected bioactive phytochemicals from P. grandiflorus that target the cellular TMPRSS2 could offer an alternative treatment option against SARS-CoV-2 infections.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies Topics: Traditional medicine Language: English Journal: J King Saud Univ Sci Year: 2022 Document Type: Article Affiliation country: J.jksus.2022.102155

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies Topics: Traditional medicine Language: English Journal: J King Saud Univ Sci Year: 2022 Document Type: Article Affiliation country: J.jksus.2022.102155