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Ligand and Structure-based Virtual Screening of Lamiaceae Diterpenes with Potential Activity against a Novel

Gabriela Cristina Soares Rodrigues¹, Mayara Dos Santos Maia¹, Renata Priscila Barros de Menezes¹

¹Laboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraiba, Joao Pessoa-PB, Brazil.

Current Topics in Medicinal Chemistry

|July 18, 2020

Insights

Computational screening identified 19 potential diterpene inhibitors for coronaviruses (CoVs), including SARS and MERS. These compounds, derived from Nepetoideae, showed no toxicity in preliminary evaluations, offering new avenues for antiviral drug discovery.

Area of Science:

Medicinal Chemistry
Computational Biology
Natural Products Chemistry

Background:

Coronaviruses (CoVs), including SARS and MERS, pose significant global health threats.
Previous CoV outbreaks highlight the urgent need for effective antiviral treatments.
Diterpenes from natural products are explored as potential therapeutic resources against CoVs.

Purpose of the Study:

To conduct virtual screening of diterpenes for potential coronavirus inhibition.
To identify novel diterpene compounds with antiviral properties against CoVs.

Main Methods:

Utilized the SistematX tool to select 1,955 diterpenes from the Nepetoideae subfamily.
Employed computational methods, including ligand- and structure-based virtual screening (VS).
Selected chemical structures from the ChEMBL database for predictive model construction.

Main Results:

Classified molecules based on pIC50 values for activity against SARS-CoV.
Identified 19 compounds as potential CoV inhibitors through consensus analysis.
Evaluated selected compounds for toxicity within defined parameters.

Conclusions:

The study identified 19 promising diterpene compounds as potential CoV inhibitors.
Isotanshinone IIA, tanshinlactone, isocryptotanshinone, and tanshinketolactone were among the top candidates.
These selected compounds demonstrated no observed toxicity, suggesting their potential for further development.

Read full analysis

Abstract

Background:

The emergence of a new coronavirus (CoV), named 2019-nCoV, as an outbreak originated in the city of Wuhan, China, has resulted in the death of more than 3,400 people this year alone and has caused worldwide an alarming situation, particularly following previous CoV epidemics, including the Severe Acute Respiratory Syndrome (SARS) in 2003 and the Middle East Respiratory Syndrome (MERS) in 2012. Currently, no exists for infections caused by CoVs; however, some natural products may represent potential treatment resources, such as those that contain diterpenes.

Objective:

This study aimed to use computational methods to perform a virtual screening (VS) of candidate diterpenes with the potential to act as CoV inhibitors.

Methods:

1,955 diterpenes, derived from the Nepetoideae subfamily (Lamiaceae), were selected using the SistematX tool (https://sistematx.ufpb.br), which were used to make predictions. From the ChEMBL database, 3 sets of chemical structures were selected for the construction of predictive models.

Results:

The chemical structures of molecules with known activity against SARS CoV, two of which were tested for activity against specific viral proteins and one of which was tested for activity against the virus itself, were classified according to their pIC50 values [-log IC50 (mol/l)].

Conclusion:

In the consensus analysis approach, combining both ligand- and structure-based VSs, 19 compounds were selected as potential CoV inhibitors, including isotanshinone IIA (01), tanshinlactone (02), isocryptotanshinone (03), and tanshinketolactone (04), which did not present toxicity within the evaluated parameters.

Keywords:

Consensus analysis Coronavirus Diterpenes Ligand Natural products database Virtual screening

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