Virtual Screening on Indonesian Herbal Compounds as COVID-19 Supportive Therapy: Machine Learning and Pharmacophore Modeling Approaches

Abstract

Background Status of the latest developments from the spread of COVID-19 in Indonesia has reached 15438 cases with 1028 cases of patients died, updated on May 13, 2020. Unfortunately, the number of infected continues to overgrow, and no drugs have been approved for effective treatment. This research aims to find potential candidate compounds in Indonesian herbal as COVID-19 supportive therapy using machine learning and pharmacophore modeling approach. Methods For a machine learning approach, we used three classification methods that have different principles in decision making, such as SVM, MLP, and Random Forest. By using these different methods, it is expected that more optimal screening results can be obtained than using only one method. Moreover, for a pharmacophore modeling approach, we did the structure-based method on the 3D structure of SARS-CoV-2 main protease (3CLPro) and using known SARS, MERS, and SARS-CoV-2 repurposing drugs from literature as data sets on the ligand-based method. Lastly, we used molecular docking to analyse the interaction between 3CLpro (main protease) protein with 14 hit compounds from the Indonesian Herbal Database (HerbalDB) and Lopinavir as a positive control. Results The models yielded by SVM, RF, and MLP were used for screening in herbal compounds obtained from HerbalDB and got 125 potential compounds. Whereas the structure-based pharmacophore modeling gave eight hit compounds and the ligand-based methods produced more than a hundred hit compounds. Based on the screening on HerbalDB using these two prediction approaches, we got 14 hit compounds candidates. Further analysis was done using molecular docking to know the interaction between each compound and main protease of SARS-CoV-2 as inhibitory agents. From molecular docking analysis, we got six potential compounds as the main protease of SARS-CoV-2 inhibitor, i.e Hesperidin, Kaempferol-3,4'-di-O-methyl ether (Ermanin); Myricetin-3-glucoside, Peonidine 3-(4’-arabinosylglucoside); Quercetin 3-(2G-rhamnosylrutinoside); and Rhamnetin 3-mannosyl-(1–2)-alloside. Conclusions Herbal compounds from various plants were potential as candidates of SARS-CoV-2 antivirals. Based on our research and literature study, one of the potential commodity crops in Indonesia is Psidium guajava (guava) and can be directly used by the community.

Differential hierarchical metabolites expression of red/white Salacca sumatrana arillus and its molecular docking studies

“…The virus that is formed then undergoes exocytosis and allows it to infect other cells. The important structure of the virus, namely the 3D structure of SARS-CoV-2 main protease (3CLPro), is reported to be inhibited by compounds contained in medicinal guava and citrus plants based on a molecular docking study by Erlina et al (2020). This study adds to the findings that S. sumatrana as a tropical medicinal plant also has the potential as a protein protease inhibitor in the SARS-Cov-2 virus based on this preliminary molecular docking study.…”

“…Metabolomics data were obtained, analyzed, and compared with Pharmacophore Modeling and Molecular Docking data from Erlina et al (2020). Metabolomics data that have potential as herbs in inhibiting the Coronavirus, especially the 3CLPro, PLPro, and RdRp proteins.…”

Drug-Target Interaction Prediction in Coronavirus Disease 2019 Case Using Deep Semi-Supervised Learning Model

“…The inputs move across the network through layers that calculate the output probabilities. Each hidden layer maps the inputs from the previous layer (xj) to the output (yj) which will be sent to the subsequent layer as in (6).…”

“…Herbal medicines tend to be more easily accessed and used by the Indonesian people in the foreseeable future. Therefore, the development of herbal medicines is necessary [6].…”

Principales plantas medicinales disponibles en Guatemala con actividad contra virus respiratorios que infectan al ser humano – Revisión narrativa

“…Tiene actividad antiviral por mecanismos de inhibición de la proteína de superficie (Dewi et al, 2019), transcriptasa inversa, neuraminidasa y proteasa (Sriwilaijaroen, et al, 2012). Sus hojas inhiben virus dengue (Abdul Kadir et al, 2013;Saptawati et al, 2017;Trujillo-Correa et al, 2019), VIA inclusive cepas H1N1 resistentes a oseltamivir (Sriwilaijaroen, et al, 2012), VIH (Umbara et al, 2015;Ortega et al, 2017), Zika (Vista et al, 2020) y en un tamizaje por docking molecular de 125 compuestos vegetales fue la más efectiva contra virus SARS, MERS y SARS-CoV-2 (Erlina et al, 2020). Sus moléculas bioactivas son flavonoides (avicularina, guajaverina, hesperidina, hiperósido, quercetina), terpenos y antocianinas (DaKappa et al, 2013).…”