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

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.

Progress and Impact of Latin American Natural Product Databases

“…In the fourth VS study, 1955 diterpenes on SistematX were employed to search for compounds against SARS-CoV-2. Nineteen compounds were identified as potential SARS-CoV-2 inhibitors [ 145 ]. In the most recent VS campaign, the researchers were seeking acetylcholinesterase (AChE) inhibitors, which is an approach for the treatment of Alzheimer’s disease.…”

Progress and Impact of Latin American Natural Product Databases

“…In the fourth VS study, 1955 diterpenes of SistematX were employed to search for compounds against SARS-CoV-2. 19 compounds were identified as potential SARS-CoV-2 inhibitors [144]. In the most recent VS campaign, the researchers were seeking for acetylcholinesterase (AChE) inhibitors, which is an approach for the treatment of Alzheimer's disease.…”

Natural and Nature-Derived Products Targeting Human Coronaviruses

“…Regarding 3CL pro , recent efforts, have identified potential inhibitors among: alkaloids [133][134][135][136][137][138], and especially indole alkaloids [139][140][141][142][143][144]; terpenoids [138], and especially diterpenes [133,145]; sesquiterpenes [134,146,147], sesquiterpene lactones [148], and triterpenes [133,136,140,149]; anthocyanins [150,151] and proanthocyanidins [152,153]; ellagitannins [153,154]; flavonoids [133,137,140,144,147,148,152,[155][156][157][158][159][160][161], biflavonoids [162], and macrocyclic flavonoids [148]; isoflavones [144,148]; chalcones...…”