Dataset Information

Identification of potential SARS-CoV-2 inhibitors from South African medicinal plant extracts using molecular modelling approaches.

ABSTRACT: The coronavirus is a group of viruses found in animals as well as humans and have been detected since the 1960s. However, a newly identified form, SARS-CoV-2, has triggered a recent pandemic of respiratory disease now called COVID-19. There is currently no specific antiviral drug for the treatment of this pandemic, with most treatment strategies focused on symptomatic management and supportive therapy. As such, several drug discovery efforts are ongoing for potent treatment agents, with medicinal plants gradually gaining prominence. Approximately 80% of the South African population use traditional medicines to meet their primary health care needs. The current study aimed to identify potential COVID-19 therapeutic agents from a list of 29 bioactive compounds isolated from commonly used South African medicinal plants using molecular docking and molecular dynamics. Molecular docking identified arabic acid from Acacia senegal and L-canavanine found in Sutherlandia frutescens as a potential inhibitor of SARS-CoV-2 3C-like main protease. Similarly, hypoxoside isolated from Hypoxis hemerocallidea and uzarin from Xysmalobium undulatum, were identified as a potential inhibitor of SARS-CoV-2 receptor binding domain and SARS-CoV-2 RNA-dependent polymerase. These four bioactive compounds exhibited favourable binding orientations characterized by strong molecular interactions within respective inhibitors binding pockets of the target enzymes. Molecular dynamics simulations revealed that the binding of the identified inhibitors are characterized by structural perturbations which favour the inhibitory potency of these bioactive compounds. Additionally, in silico pharmacokinetic assessment of the compounds demonstrated favourable anti-SARS-CoV-2 properties. Although not conclusive, further experimental exploration of these compounds could serve as a starting point for the discovery of novel SARS-CoV-2 therapeutic.

SUBMITTER: Dwarka D

PROVIDER: S-EPMC7437493 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of potential SARS-CoV-2 inhibitors from South African medicinal plant extracts using molecular modelling approaches.

Dwarka Depika D Agoni Clement C Mellem John Jason JJ Soliman Mahmoud E ME Baijnath Himansu H

South African journal of botany : official journal of the South African Association of Botanists = Suid-Afrikaanse tydskrif vir plantkunde : amptelike tydskrif van die Suid-Afrikaanse Genootskap van Plantkundiges 20200819

The coronavirus is a group of viruses found in animals as well as humans and have been detected since the 1960s. However, a newly identified form, SARS-CoV-2, has triggered a recent pandemic of respiratory disease now called COVID-19. There is currently no specific antiviral drug for the treatment of this pandemic, with most treatment strategies focused on symptomatic management and supportive therapy. As such, several drug discovery efforts are ongoing for potent treatment agents, with medicina ...[more]

PMID: 32839635

Similar Datasets

Project description:BackgroundInfluenza infection remains a major health threat for animals and humans which crucially requires effective antiviral remedies. The usage of herbal medications as readily available alternatives for their compatibility with the body and fewer side effects compared to synthetic chemical treatments has become popular globally. The aim of this study was to investigate and screen in vitro anti-influenza activity of extracts of five South African medicinal plants, namely Tabernaemontana ventricosa, Cussonia spicata, Rapanea melanophloeos, Pittosporum viridiflorum and Clerodendrum glabrum, species which are used traditionally for the treatment of several diseases such as inflammatory and respiratory diseases.MethodsMethanol, ethanol (100% and 30%), acetone, hot and cold water extracts of the powdered plants leaves were obtained by standard methods. The cytotoxicity was determined by the MTT colorimetric assay on MDCK cells. The concentrations below CC50 values were tested for antiviral activity against influenza A virus (IAV) in different combination treatments. The effect of extracts on viral surface glycoproteins and viral titer were tested by HI and HA virological assays, respectively.ResultsBased on the applied methods, the most effective results against IAV were obtained from Rapanea melanophloeos methanol leaf extract (EC50?=?113.3 ?g/ml) and Pittosporum viridiflorum methanol, 100% and 30% ethanol and acetone leaf extracts (EC50 values?=?3.6, 3.4, 19.2, 82.3 ?g/ml, respectively) in all types of combined treatments especially in pre- and post-penetration combined treatments with highly significant effects against viral titer (P???0.01).ConclusionThe outcomes offer for the first time a scientific basis for the use of extracts of Rapanea melanophloeos and Pittosporum viridiflorum against IAV. It is worth focusing on the isolation and identification of effective active compounds and elucidating the mechanism of action from these species. However, Tabernaemontana ventricosa, Cussonia spicata and Clerodendrum glabrum leaf extracts were ineffective in vitro in this study.

Project description:Background:Medicinal plants are used by a large proportion of the global population as complementary and alternative medicines. However, little is known about their toxicity. G. africana has been used to treat wounds, coughs and skin diseases and is used in cosmetic formulations such as lotions and shampoos. Methods:The acute oral and dermal toxicity potential of G. africana was analyzed after a single administration of 300 and 2000?mg/kgbw for acute oral toxicity and 2000?mg/kgbw for acute dermal toxicity. Female Sprague-Dawley rats were used for the acute oral toxicity study whereas both male and female Sprague-Dawley rats were used for the acute dermal toxicity study. In the Episkin skin irritation test, the irritation potential of G. africana (concentrate) and G. africana (in-use dilution) extracts were assessed using the Episkin reconstituted human epidermis. In the dermal sensitization study, female CBA/Ca mice were treated with G. africana concentrations of 50, 100 and 200?mg/ml respectively. The vehicle of choice was dimethylformamide which acted as a control. Results:The results of the acute oral and dermal toxicity studies revealed that the median lethal dosage (LD50) for G. africana extract in Sprague-Dawley rats was considered to exceed 2000?mg/kgbw. In the irritation test, the G. africana (concentrate) and G. africana (in-use dilution) extracts were non-irritant on the Episkin reconstituted human epidermis. In the dermal sensitization study, the stimulation index (SI) values for the mice treated with the G. africana extract at concentrations of 50, 100 and 200?mg/ml/kgbw, when compared to the control group, were 1.3, 0.9 and 1.3 respectively. The open application of the extract at the various concentrations did not result in a SI of ? 3 in any group. Hence, it did not elicit a hypersensitivity response. Conclusion:These findings demonstrate that the acute toxicity profile for G. africana is acceptable and can subsequently be used for single use in the pharmaceutical and cosmetic industries.

Project description:The emergence of multidrug-resistant (MDR) Klebsiella pneumoniae remains a global health threat due to its alarming rates of becoming resistant to antibiotics. Therefore, identifying plant-based treatment options to target this pathogen's virulence factors is a priority. This study examined the antivirulence activities of twelve plant extracts obtained from three South African medicinal plants (Lippia javanica, Carpobrotus dimidiatus, and Helichrysum populifolium) against carbapenem-resistant (CBR) and extended-spectrum beta-lactamase (ESBL) positive K. pneumoniae strains. The plant extracts (ethyl acetate, dichloromethane, methanol, and water) were validated for their inhibitory activities against bacterial growth and virulence factors such as biofilm formation, exopolysaccharide (EPS) production, curli expression, and hypermucoviscosity. The potent extract on K. pneumoniae biofilm was observed with a scanning electron microscope (SEM), while exopolysaccharide topography and surface parameters were observed using atomic force microscopy (AFM). Chemical profiling of the potent extract in vitro was analysed using liquid chromatography-mass spectrometry (LC-MS). Results revealed a noteworthy minimum inhibitory concentration (MIC) value for the C. dimidiatus dichloromethane extract at 0.78 mg/mL on CBR- K. pneumoniae. L. javanica (ethyl acetate) showed the highest cell attachment inhibition (67.25%) for CBR- K. pneumoniae. SEM correlated the in-vitro findings, evidenced by a significant alteration of the biofilm architecture. The highest EPS reduction of 34.18% was also noted for L. javanica (ethyl acetate) and correlated by noticeable changes observed using AFM. L. javanica (ethyl acetate) further reduced hypermucoviscosity to the least length mucoid string (1 mm-2 mm) at 1.00 mg/mL on both strains. C. dimidiatus (aqueous) showed biofilm inhibition of 45.91% for the ESBL-positive K. pneumoniae and inhibited curli expression at 0.50 mg/mL in both K. pneumoniae strains as observed for H. populifolium (aqueous) extract. Chemical profiling of L. javanica (ethyl acetate), C. dimidiatus (aqueous), and H. populifolium (aqueous) identified diterpene (10.29%), hydroxy-dimethoxyflavone (10.24%), and 4,5-dicaffeoylquinic acid (13.41%), respectively, as dominant compounds. Overall, the ethyl acetate extract of L. javanica revealed potent antivirulence properties against the studied MDR K. pneumoniae strains. Hence, it is a promising medicinal plant that can be investigated further to develop alternative therapy for managing K. pneumoniae-associated infections.

Dataset Information

Identification of potential SARS-CoV-2 inhibitors from South African medicinal plant extracts using molecular modelling approaches.

Publications

Identification of potential SARS-CoV-2 inhibitors from South African medicinal plant extracts using molecular modelling approaches.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets