Brazilian essential oils as source for the discovery of new anti-COVID-19 drug: a review guided by in silico study

Abstract

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China and its spread worldwide has become one of the biggest health problem due to the lack of knowledge about an effective chemotherapy. Based on the current reality of the SARS-CoV-2 pandemic, this study aimed to make a review literature about potential anti-coronavirus natural compounds guided by an in silico study. In the first step, essential oils from native species found in the Brazilian herbal medicine market and Brazilian species that have already shown antiviral potential were used as source for the literature search and compounds selection. Among these compounds, 184 showed high antiviral potential against rhinovirus or picornavirus by quantitative structure-activity relationship analysis. (E)-α-atlantone; 14-hydroxy-α-muurolene; allo-aromadendrene epoxide; amorpha-4,9-dien-2-ol; aristochene; azulenol; germacrene A; guaia-6,9-diene; hedycaryol; humulene epoxide II; α-amorphene; α-cadinene; α-calacorene and α-muurolene showed by a molecular docking study the best result for four target proteins that are essential for SARS-CoV-2 lifecycle. In addition, other parameters obtained for the selected compounds indicated low toxicity and showed good probability to achieve cell permeability and be used as a drug. These results guided the second literature search which included other species in addition to native Brazilian plants. The majority presence of any of these compounds was reported for essential oils from 45 species. In view of the few studies relating essential oils and antiviral activity, this review is important for future assays against the new coronavirus.

Supplementary information: The online version contains supplementary material available at 10.1007/s11101-021-09754-4.

Keywords: Brazilian species; COVID-19; Coronavirus; Essential oil; SARS-CoV-2; Terpene.

Fig. 1

Workflow scheme. The work is divided into four main parts: (1) Search of natural compounds present in essential oils from Brazilian native species; (2) QSAR analysis and selection of compounds with high antiviral potential; (3) Molecular docking analysis and selection of top 14 compounds with the highest binding energies values for papain-like protease (PLpro), 3-Chymotrypsin-like protease (3CLpro), spike glycoprotein (S protein), and RNA-dependent RNA polymerase (RdRp); (4) Search of species containing at least one of selected compounds as top 5 constituent in their essential oil

Fig. 2

(1) (E)-α-Atlantone; (2) 14-Hydroxy-α-muurolene; (3) allo-Aromadendrene epoxide; (4) Amorpha-4,9-dien-2-ol; (5) Aristochene; (6) Azulenol; (7) Germacrene A; (8) Guaia-6,9-diene; (9) Hedycaryol; (10) Humulene epoxide II; (11) α-Amorphene; (12) α-Cadinene; (13) α-Calacorene; (14) α-Muurolene

Fig. 3

3D diagram showing the superimposed binding site of compounds from essential oils and controls with a spike glycoprotein (S protein), b papain-like protease (PLpro), c 3-Chymotrypsin-like protease (3CLpro) and d RNA-dependent RNA polymerase (RdRp). (1) (E)-α-Atlantone; (2) 14-Hydroxy-α-muurolene; (3) allo-Aromadendrene epoxide; (4) Amorpha-4,9-dien-2-ol; (5) Aristochene; (6) Azulenol; (7) Germacrene A; (8) Guaia-6,9-diene; (9) Hedycaryol; (10) Humulene epoxide II; (11) α-Amorphene; (12) α-Cadinene; (13) α-Calacorene; (14) α-Muurolene; (HCQ) hydroxychloroquine; (ARB) arbidol; (FMT) formoterol; (DSF) disulfiram; (PFX) prulifloxacin; (NFN) nelfinavir; (RDS) remdesivir and (FVP) favipiravir. ^aEnergy binding energy values in kcal/mol (unnormalized)