Skip to content
Research Article Open access CC BY 4.0

In-silico ADME and Docking-based Virtual Screening Study Aiming at the Sigma-Covalent Inhibition of SARS-CoV-2 RdRp

G. Koteswara Reddy, V. Nikhil Reddy, S. Phavethra, A. Bhavani, A. J. Vineeth, A. V. V. Satish Reddy

Journal of Pharmaceutical Research International · pp. 321–336 · Published 13 Dec 2021

10.9734/jpri/2021/v33i54B33795

Abstract

The objectives of the study were to examine the virtual screening of the compounds and sigma-covalent inhibition of SARS-CoV-2 RdRp (RNA-Dependent RNA-Polymerase), which is conserved and is an essential enzyme for RNA transcription and replication of this virus. In this study, we collected around 1225 similar compounds of Penciclovir and Acyclovir inhibitors from PubChem and predicted ADME (Adsorption, Distribution, Metabolism and Excretion) molecular descriptors using Swiss-ADME server. Virtually screened 24/1225 compounds based on drug-likeliness five rules (Lipinski, Ghose, Veber, Egan, and Muegge) and lead-likeliness properties. Further 10/24 compounds screened, based on high binding affinity and RMSD<3.5Å against RdRp structure using PyRx docking software. Furthermore, the molecular interactions of 10 compounds studied using Discovery studio software and finally screened five PubChem compounds 57201841, 135408972, 54552823, 135409422 and 467850, based on bioactivity score using Molinsipiration cheminformatics software. All these five compounds showed up anti-SARS CoV-2 activity, though further in-vitro studies are required.

SARS-CoV-2 RdRp Penciclovir Acyclovir Swiss-ADME

References (20)

  1. 1 A Novel Coronavirus from Patients with Pneumonia in China, 2019 [DOI]
  2. 2 A pneumonia outbreak associated with a new coronavirus of probable bat origin [DOI]
  3. 3 Open Babel: An open chemical toolbox [DOI]
  4. 4 Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro [DOI]
  5. 5 Simple Selection Criteria for Drug-like Chemical Matter [DOI]
  6. 6 Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors [DOI]
  7. 7 Relative Binding Free Energy Calculations in Drug Discovery: Recent Advances and Practical Considerations [DOI]
  8. 8 The Design of Leadlike Combinatorial Libraries [DOI]
  9. 9 Structure-Based Drug Design: Docking and Scoring [DOI]
  10. 10 A second, non‐canonical RNA‐dependent RNA polymerase in SARS Coronavirus [DOI]
  11. 11 The 2019 novel coronavirus disease (COVID-19) pandemic [DOI]
  12. 12 SARS-CoV ORF1b-encoded nonstructural proteins 12–16: Replicative enzymes as antiviral targets [DOI]
  13. 13 Identification of FDA approved drugs against SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and 3-chymotrypsin-like protease (3CLpro), drug repurposing approach [DOI]
  14. 14 Progress in Anti-SARS Coronavirus Chemistry, Biology and Chemotherapy [DOI]
  15. 15 Antiviral Activity of Nucleoside Analogues against SARS-coronavirus (SARS-CoV) [DOI]
  16. 16 SARS-CoV-2 main protease inhibition by compounds isolated from Luffa cylindrica using molecular docking [DOI]
  17. 17 Docking-based virtual screening studies aiming at the covalent inhibition of SARS-CoV-2 MPro by targeting the cysteine 145 [DOI]
  18. 18 In silico ADME, Bioactivity and Toxicity Parameters Calculation of Some Selected Anti-Tubercular Drugs [DOI]
  19. 19 In silico study for evaluating the binding mode and interaction of 1, 2, 4-triazole and its derivatives as potent inhibitors against Lipoate protein B (LipB) [DOI]
  20. 20 Structure of the SARS-CoV NSP12 polymerase bound to NSP7 and NSP8 co-factors [DOI]

Cited by 6

Exploring Bioactive Compounds of Rauvolfia tetraphylla L. (RT) for 3CLprotease of SARS-CoV2: GC-MS Analysis and In-Silico Studies

Gnanasekaran Ramakrishnan, Koteswara Reddy Gujjula, Janaki Ramaiah Mekala · Cell Biochemistry and Biophysics · 2024

Showing 3 of 6 known citations — external sources report more than can currently be individually listed.

Article metrics

Real usage data collected on this platform.

0

Page views

0

PDF downloads

0

Outbound clicks

6

Citations

Views by country

Approximate, from request IP at view time — not citizenship or institution. Countries with fewer than 5 views are grouped as "Other".

No views recorded yet.

Traffic sources

Referring site, by host.

No traffic recorded yet.

Views and downloads exclude known bots/crawlers. Citations combines this platform's own DOI-resolved index with each external source's own reported total — see Cited by above for individually listed citing works. Last refreshed 0 seconds ago.