Curr Top Med Chem . Ligand- and structure-based virtual screening of Lamiaceae diterpenes with potential activity against a novel coronavirus (2019-nCoV)

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Curr Top Med Chem


. 2020 Jul 15.
doi: 10.2174/1568026620666200716114546. Online ahead of print.
Ligand- and structure-based virtual screening of Lamiaceae diterpenes with potential activity against a novel coronavirus (2019-nCoV)


Gabriela Cristina Soares Rodrigues ¹ , Mayara Dos Santos Maia ¹ , Renata Priscila Barros de Menezes ¹ , Andreza Barbosa Silva Cavalcanti ¹ , Nat?lia Ferreira de Sousa ¹ , ?rika Paiva de Moura ¹ , Alex France Messias Monteiro ¹ , Luciana Scotti ¹ , Marcus Tullius Scotti ¹



Affiliations

• PMID: 32674732
• DOI: 10.2174/1568026620666200716114546

Abstract

Background: The emergence of a new coronavirus (CoV), named 2019-nCoV, in an outbreak located in the city of Wuhan, China, has resulted in the death more than 3,400 people this year alone and has caused worldwide alarm, particularly following previous CoV epidemics, including the Severe Acute Respiratory Syndrome (SARS) in 2003 and the Middle East Respiratory Syndrome (MERS) in 2012. No treatment currently 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 screen (VS) of candidate diterpenes with the potential to act as CoV inhibitors.
Methods: 1,955 diterpenes, derived from a 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: 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.