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Ligand and Structure-based Virtual Screening of Lamiaceae Diterpenes with Potential Activity against a Novel Coronavirus (2019-nCoV)

[ Vol. 20 , Issue. 24 ]

Author(s):

Gabriela Cristina Soares Rodrigues, Mayara dos Santos Maia, Renata Priscila Barros de Menezes, Andreza Barbosa Silva Cavalcanti, Natália Ferreira de Sousa, Érika Paiva de Moura, Alex France Messias Monteiro, Luciana Scotti and Marcus Tullius Scotti*   Pages 2126 - 2145 ( 20 )

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:

Coronavirus, Virtual screening, Natural products database, Diterpenes, Consensus analysis, Ligand.

Affiliation:

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

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