Virtual screening and in vitro validation of natural compound inhibitors against SARS-CoV-2 spike protein.

Helen Power, Jiadai Wu, Stuart Turville, Anupriya Aggarwal, Peter Valtchev, Aaron Schindeler, Fariba Dehghani

Open access · greenAbstract read

In one paragraph

Article in Bioorganic chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it

0cells of the map it votes in

11citing papers in PubMed

2.0field-weighted citation impact, top 12% of its field

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 16 citations in OpenAlex.

Identification and validation of natural product-based KRASMolecular diversity · 2026
Article
Structure-Based Screening of Antiviral Candidates Against Infectious Spleen and Kidney Necrosis Virus (ISKNV) Using Molecular Docking andBiomolecules · 2026
Article
In silico pharmacological analysis of Tinospora cordifolia compounds targeting African swine fever virus B175L.PloS one · 2026
Article
Computational Evaluation and Multi-Criteria Optimization of Natural Compound Analogs Targeting SARS-CoV-2 Proteases.Current issues in molecular biology · 2025
Article
Molecular Docking and ADME-TOX Profiling ofAdvances in respiratory medicine · 2023
Article
Identification of potential Indonesian marine invertebrate bioactive compounds as TMPRSS2 and SARS-CoV-2 Omicron spike protein inhibitors through computational screening.Arabian journal of chemistry · 2023
Article
Coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 helicase inhibitors: a systematic review ofJournal of virus eradication · 2023
Review
Identification of Potent Zika Virus NS5 RNA-Dependent RNA Polymerase Inhibitors Combining Virtual Screening and Biological Assays.International journal of molecular sciences · 2023
Article
Development of spiro-3-indolin-2-one containing compounds of antiproliferative and anti-SARS-CoV-2 properties.Scientific reports · 2022
Article
Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2.Chemical reviews · 2022
Review
Structure based Drug Designing Approaches in SARS-CoV-2 Spike Inhibitor Design.Current topics in medicinal chemistry · 2022
Review

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Helen PowerSchool of Chemical and Biomolecular Engineering, Faculty of Engineering, The University of Sydney, Sydney, NSW 2006, Australia; Centre for Advanced Food Engineering, The University of Sydney, Sydney, NSW 2006, Australia; Bioengineering and Molecular Medicine Laboratory, The Children's Hospital at Westmead and Westmead Institute for Medical Research, Westmead, NSW 2145, Australia.

Jiadai WuSchool of Chemical and Biomolecular Engineering, Faculty of Engineering, The University of Sydney, Sydney, NSW 2006, Australia; Centre for Advanced Food Engineering, The University of Sydney, Sydney, NSW 2006, Australia.

Stuart TurvilleThe Kirby Institute, University of NSW, Kensington, NSW 2052, Australia.

Anupriya AggarwalThe Kirby Institute, University of NSW, Kensington, NSW 2052, Australia.

Peter ValtchevSchool of Chemical and Biomolecular Engineering, Faculty of Engineering, The University of Sydney, Sydney, NSW 2006, Australia; Centre for Advanced Food Engineering, The University of Sydney, Sydney, NSW 2006, Australia.

Aaron SchindelerSchool of Chemical and Biomolecular Engineering, Faculty of Engineering, The University of Sydney, Sydney, NSW 2006, Australia; Centre for Advanced Food Engineering, The University of Sydney, Sydney, NSW 2006, Australia; Bioengineering and Molecular Medicine Laboratory, The Children's Hospital at Westmead and Westmead Institute for Medical Research, Westmead, NSW 2145, Australia.

Fariba DehghaniSchool of Chemical and Biomolecular Engineering, Faculty of Engineering, The University of Sydney, Sydney, NSW 2006, Australia; Centre for Advanced Food Engineering, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: fariba.dehghani@sydney.edu.au.

University of Sydney · AUWestmead Institute for Medical Research · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to a major public health burden and has resulted in millions of deaths worldwide. As effective treatments are limited, there is a significant requirement for high-throughput, low resource methods for the discovery of novel antivirals. The SARS-CoV-2 spike protein plays a key role in viral entry and has been identified as a therapeutic target. Using the available spike crystal structure, we performed a virtual screen with a library of 527 209 natural compounds against the receptor binding domain of this protein. Top hits from this screen were subjected to a second, more comprehensive molecular docking experiment and filtered for favourable ADMET properties. The in vitro activity of 10 highly ranked compounds was assessed using a virus neutralisation assay designed to facilitate viral entry in a physiologically relevant manner via the plasma membrane route. Subsequently, four compounds ZINC02111387, ZINC02122196, SN00074072 and ZINC04090608 were identified to possess antiviral activity in the µM range. These findings validate the virtual screening method as a tool for identifying novel antivirals and provide a basis for future drug development against SARS-CoV-2.

Indexed as

AnimalsAntiviral AgentsBiological ProductsComputer SimulationDrug Evaluation, PreclinicalHumansModels, MolecularMolecular Docking SimulationMolecular Dynamics SimulationNeutralization TestsReproducibility of ResultsSARS-CoV-2Spike Glycoprotein, CoronavirusVirus InternalizationAntiviral AgentsBiological ProductsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2COVID-19Molecular modelingNatural compound inhibitorSARS-CoV-2Virus neutralization assay

Identifiers

PMID34971947

DOI10.1016/j.bioorg.2021.105574

PMCPMC8693770

OpenAlexW4200215886

What OpenQuestion holds

Textmetadata

Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.