Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Structure-Activity Relationships and Drug Design01:28

Structure-Activity Relationships and Drug Design

597
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
597
Drug Discovery: Overview01:26

Drug Discovery: Overview

7.5K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
7.5K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Synthesis and Evaluation of Nitroheterocyclic Aromatic Adamantanohydrazones with Trypanocidal Activity. Part III.

ACS infectious diseases·2026
Same author

The love and hate relationship between cellular senescence and stemness.

Aging·2026
Same author

Mirroring tissue senescence in human biofluids.

Nature aging·2026
Same author

Electrophilic compound screening identifies GPX4-dependent ferroptosis as a senescence vulnerability.

Nature cell biology·2026
Same author

Bio-Compatibility Analysis of Newly Developed Plug and Cuff Electrodes for Future Neuronal Interface Applications.

Biomimetics (Basel, Switzerland)·2026
Same author

Interpreting the Theranostic Applications of Alumina and Silica Substrates in Cancer.

Molecules (Basel, Switzerland)·2026

Related Experiment Video

Updated: Jun 7, 2025

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

426

AI Promoted Virtual Screening, Structure-Based Hit Optimization, and Synthesis of Novel COVID-19 S-RBD Domain

Ioannis Gkekas1, Sotirios Katsamakas2,3, Stelios Mylonas2

  • 1Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki 57001, Greece.

Journal of Chemical Information and Modeling
|November 13, 2024
PubMed
Summary

Researchers identified a novel benzimidazole derivative, CKP-25, that effectively inhibits SARS-CoV-2 entry into cells. This compound shows promise as a potential therapeutic agent against COVID-19 by blocking the spike protein-ACE2 interaction.

More Related Videos

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source
08:35

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source

Published on: May 29, 2021

5.1K
Assays for the Identification of Novel Antivirals against Bluetongue Virus
12:02

Assays for the Identification of Novel Antivirals against Bluetongue Virus

Published on: October 11, 2013

14.0K

Related Experiment Videos

Last Updated: Jun 7, 2025

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

426
Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source
08:35

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source

Published on: May 29, 2021

5.1K
Assays for the Identification of Novel Antivirals against Bluetongue Virus
12:02

Assays for the Identification of Novel Antivirals against Bluetongue Virus

Published on: October 11, 2013

14.0K

Area of Science:

  • Virology
  • Drug Discovery
  • Computational Chemistry

Background:

  • Severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) utilizes its spike (S) glycoprotein to bind to the angiotensin-converting enzyme II (ACE2) receptor on host cells, facilitating viral entry.
  • Targeting the S protein-ACE2 interaction presents a viable strategy for developing antiviral therapies against Coronavirus disease 2019 (COVID-19).

Purpose of the Study:

  • To identify small molecules capable of inhibiting the interaction between the SARS-CoV-2 S protein's receptor-binding domain (RBD) and the human ACE2 receptor.
  • To discover and optimize lead compounds with potential antiviral activity against SARS-CoV-2.

Main Methods:

  • Virtual screening of large compound libraries using an AI-based pipeline to identify molecules that bind to the SARS-CoV-2 RBD.
  • In vitro assays to evaluate the inhibitory effects of identified compounds on Spike RBD/ACE2 interaction and viral infection.
  • Hit-to-lead optimization through synthesis of derivatives and subsequent in vitro ADME-Tox profiling.

Main Results:

  • Initial screening yielded 31 hit compounds, with six demonstrating dose-dependent inhibition of S-ACE2 interaction.
  • Two compounds prevented pseudotyped viral infection, and one, the benzimidazole derivative CKP-22, protected Vero E6 cells from SARS-CoV-2 infection.
  • Optimized derivative CKP-25 significantly suppressed S-ACE2 interaction (IC50 = 3.5 μM), reduced viral load, and exhibited favorable in vitro ADME-Tox properties, including weak CYP450 inhibition and no mutagenicity.

Conclusions:

  • CKP-25 is a potent inhibitor of SARS-CoV-2 S-ACE2 interaction and demonstrates significant antiviral activity in vitro.
  • CKP-25 possesses favorable pharmacokinetic and safety profiles, positioning it as a promising lead compound for further development as a COVID-19 therapeutic.