Virtual screening of Indonesian herbal compounds as COVID-19 supportive therapy: machine learning and pharmacophore modeling approaches

Abstract

Background The number of COVID-19 cases continues to grow in Indonesia. This phenomenon motivates researchers to find alternative drugs that function for prevention or treatment. Due to the rich biodiversity of Indonesian medicinal plants, one alternative is to examine the potential of herbal medicines to support COVID therapy. This study aims to identify potential compound candidates in Indonesian herbal using a machine learning and pharmacophore modeling approaches. Methods We used three classification methods that had different decision-making processes: support vector machine (SVM), multilayer perceptron (MLP), and random forest (RF). For the pharmacophore modeling approach, we performed a structure-based analysis on the 3D structure of the main protease SARS-CoV-2 (3CLPro) and repurposed SARS, MERS, and SARS-CoV-2 drugs identified from the literature as datasets in the ligand-based method. Lastly, we used molecular docking to analyze the interactions between the 3CLpro and 14 hit compounds from the Indonesian Herbal Database (HerbalDB), with lopinavir as a positive control. Results From the molecular docking analysis, we found six potential compounds that may act as the main proteases of the SARS-CoV-2 inhibitor: hesperidin, kaempferol-3,4'-di-O-methyl ether (Ermanin); myricetin-3-glucoside, peonidin 3-(4’-arabinosylglucoside); quercetin 3-(2G-rhamnosylrutinoside); and rhamnetin 3-mannosyl-(1-2)-alloside. Conclusions Our layered virtual screening with machine learning and pharmacophore modeling approaches provided a more objective and optimal virtual screening and avoided subjective decision making of the results. Herbal compounds from the screening, i.e. hesperidin, kaempferol-3,4'-di-O-methyl ether (Ermanin); myricetin-3-glucoside, peonidin 3-(4’-arabinosylglucoside); quercetin 3-(2G-rhamnosylrutinoside); and rhamnetin 3-mannosyl-(1-2)-alloside are potential antiviral candidates for SARS-CoV-2. Moringa oleifera and Psidium guajava that consist of those compounds, could be an alternative option as COVID-19 herbal preventions.

Marine-Derived Bioactive Metabolites as a Potential Therapeutic Intervention in Managing Viral Diseases: Insights from the SARS-CoV-2 In Silico and Pre-Clinical Studies

“…In this regard, in silico techniques such as molecular docking, molecular dynamics simulations, and network pharmacology are useful for the preliminary identification of natural compounds that can directly inhibit target proteins [ 5 , 135 , 151 ]. Molecular docking evaluates the binding and interaction between the specified molecules (i.e., marine-derived metabolites) and the target protein(s), whereas network pharmacology employs computationally simulated drug-targeted interactions to identify potential inhibitors for a particular target and mode of action [ 152 , 153 ]. Additionally, the process evaluates the stability of the predicted protein–ligand complex considering factors such as the nature of the solvent [ 154 ].…”

COVID‐19 in early 2023: Structure, replication mechanism, variants of SARS‐CoV‐2, diagnostic tests, and vaccine & drug development studies

“…The human immune system plays a significant role in controlling the infection and replication of coronavirus. Therefore, blocking the human signaling pathways required for virus replication might show a particular antiviral effect 161 . The therapies that act on the coronavirus itself contain blocking the binding of the virus to the human cell receptors, preventing the synthesis of viruses’ RNA, inhibiting processing of the viral assembly through acting on some structural proteins, or inhibiting viral replication via acting on crucial enzymes of the virus 162 …”

Antibacterial Activity of Ginkgo biloba Extracts against Clavibacter michiganensis subsp. michiganensis, Pseudomonas spp., and Xanthomonas vesicatoria

“…[51] and T. baccata [31]. Additionally, 3-methylmannoside has been found in Psidium guajava L. [52]. None of these polysaccharides have been identified as bactericides.…”