The Study of Potential Antiviral Compounds from Indonesian Medicinal Plants as Anti-COVID-19 with Molecular Docking Approach

Corona Virus Disease 2019 (COVID-19) is a new strain of coronavirus called SARS-CoV-2, which was identified in Wuhan, China, in December 2019. The rapid transmission of COVID-19 from human to human forced researchers to find a potent drug by setting aside the time-consuming traditional method in drug development. The molecular docking approach is one a reliable method to screening compound from chemical drug or by finding a compound from Indonesian herbal plants. The present study aimed to assess the potency of compounds from five medicinal plants as potential inhibitors of PLpro and 3CLpro from SARS-CoV-2 using molecular study. The molecular docking was performed using Protein-Ligand Ant System (PLANTS) to analyze the potential compounds by the docking score. Remdesivir triphosphate was used as a standard for the comparison of the test compounds. The docking score obtained from the docking of PLpro with native ligand, remdesivir triphosphate, curcumin, demethoxycurcumin, bisdemethoxycurcumin, luteolin, apigenin, quercetin, kaempferol, formononetin-7-O-glucuronide, andrographolide, and neoandrographolide were -111.441, -103.827, -103.609, -102.363, -100.27, -79.6655, -78.6901, -80.9337, -79.4686, -82.1124, -79.1789, and -97.2452, respectively. Meanwhile, docking score with 3CLpro for the same ligand were -64.0074, -86.1811, -81.428, -87.1625, -78.2899, -73.4345, -70.3368, -71.5539, -68.4321, -72.0154, -75.9777, and -93.7746. The docking score data suggest that curcumin was the most potential as a PLpro inhibitor, while neoandrographolide was the best as a 3CLpro inhibitor.

Suitable Docking Protocol for the Design of Novel Coumarin Derivatives with Selective MAO-B Effects

Recently, the application of molecular docking is drastically increasing due to the rapid growth of resolved crystallographic receptors with co-crystallized ligands. However, the inability of docking softwares to correctly score the occurred interactions between ligands and receptors is still a relevant issue. This study examined the Pearson’s correlation coefficient between the experimental monoamine oxidase-B (MAO-B) inhibitory activity of 44 novel coumarins and the obtained GOLD 5.3 docking scores. Subsequently, optimization of the docking protocol was carried out to achieve the best possible pairwise correlation. Numerous modifications in the docking settings such as alteration in the scoring functions, size of the grid space, presence of active waters, and side-chain flexibility were conducted. Furthermore, ensemble docking simulations into two superimposed complexes were performed. The model was validated with a test set. A significant Pearson’s correlation coefficient of 0.8217 was obtained for the latter. In the final stage of our work, we observed the major interactions between the top-scored ligands and the active site of 1S3B.

Cover, Content, and Editorial Note from J Mol Docking Vol. 1 No. 1 June 2021

Assalamu’alaikum Wr. Wb.Alhamdulillahirabbil ‘alamin. After a long wait for almost 1 year from the first planned, finally, the new scientific journal of the Department of Pharmacy Universitas Muhammadiyah Palangkaraya can be published. This scientific journal was named the Journal of Molecular Docking (J Mol Docking), inspired by one of the most popular in silico methods in computer-aided drug design. Journal of Molecular Docking published every 6 months (2 issues/year) every June and December.This edition contains five articles consisting of writings from four countries including Indonesia, India, Bulgaria, and Egypt. The authors come from several institutions, including Bio Search Research Institution, Sekolah Tinggi Farmasi Muhammadiyah Tangerang, Sri Ramachandra Institute of Higher Education and Research, Siddha Central Research Institute – Central Council for Research in Siddha, Chhattisgarh Swami Vivekanand Technical University, Universitas Mataram, and Medical University – Sofia.Editorial boards are fully aware that there is still room for improvement in this edition, hence with all humility willing to accept constructive suggestions and feedback for improvements to the publication for the next editions. The editorial board would like to thank all editors and reviewers, and contributors of the scientific articles who have provided the repertoire in this issue. We hope that all parties, especially the contributors of the articles, could re-participate for publication in the next edition in December 2021.Wassalamu’alaikum Wr. Wb.

A Comparative Study of Approved Drugs for SARS-CoV-2 by Molecular Docking

SARS-CoV-2, a new type of Coronavirus, has affected more millions of people worldwide. From the spread of this infection, many studies related to this virus and drug designing for the treatment have been started. Most of the studies target the SARS-CoV-2 main protease, spike protein of SASR-CoV-2, and some are targeting the human furin protease. In the current work, we chose the clinically used drug molecules remdesivir, favipiravir, lopinavir, hydroxychloroquine, and chloroquine onto the target protein SARS-CoV-2 main protease. Docking studies were performed using Arguslab, while Discovery Studio collected 2D and 3D pose views with the crystal structure of COVID-19 main protease in complex with an inhibitor N3 with PDB ID 6LU7. Computational studies reveal that all ligands provided good binding affinities towards the target protein. Among all the chosen drugs, lopinavir showed the highest docking score of -11.75 kcal/mol. The results from this molecular docking study encourage the use of lopinavir as the first-line treatment drug due to its highest binding affinity.

Development of SARS-CoV-2 Inhibitors Using Molecular Docking Study with Different Coronavirus Spike Protein and ACE2

The novel coronavirus SARS-CoV-2 is an acute respiratory tract infection that emerged in Wuhan city, China. The spike protein of coronaviruses is the main driving force for host cell recognition and is responsible for binding to the ACE2 receptor on the host cell and mediates the fusion of host and viral membranes. Recognizing compounds that could form a complex with the spike protein (S-protein) potently could inhibit SARS-CoV-2 infections. The software was used to survey 300 plant natural compounds or derivatives for their binding ability with the SARS-CoV-2 S-protein. The docking score for ligands towards each protein was calculated to estimate the binding free energy. Four compounds showed a strong ability to bind with the S-protein (neohesperidin, quercetin 3-O-rutinoside-7-O-glucoside, 14-ketostypodiol diacetate, and hydroxypropyl methylcellulose) and used to predict its docking model and binding regions. The highest predicted ligand/protein affinity was with quercetin 3-O-rutinoside-7-O-glucoside followed by neohesperidin. The four compounds were also tested against other related coronavirus and showed their binding ability to S-protein of the bat, SARS, and MERS coronavirus strains, indicating that they could bind and block the spike activities and subsequently prevent them infection of different coronaviruses. Molecular docking also showed the probability of the four ligands binding to the host cell receptor ACE2. The interaction residues and the binding energy for the complexes were identified. The strong binding ability of the four compounds to the S-protein and the ACE2 protein indicates that they might be used to develop therapeutics specific against SARS-CoV-2 and close related human coronaviruses.

Molecular Docking Studies of Phytoconstituents Identified in Traditional Siddha Polyherbal Formulations Against Possible Targets of SARS-CoV-2

The Indian Traditional Medicines System has long used Siddha polyherbal formulations for different viral diseases. The ingredients of these formulas have been proven to be antiviral. The study focuses on in silico computational evaluation of phytoconstituents of the official Siddha formulation Kabasura, Thonthasura, and Vishasura Kudineer, which were widely used in treating viral fever and respiratory infections and may influence the current SARS-CoV-2 coronary virus pandemic. Maestro interface (Schrödinger Suite, LLC, NY) was used for molecular docking studies against MPro (PDB ID 5R82, 6Y2F, and 6LU7), Nsp15 endoribonuclease (6W01), RNA-dependent RNA polymerase (6M71), and spike protein (6VW1) of SARS-CoV-2. In addition, pharmacokinetics (ADME) and safety profile prediction studies were performed to identify the best drug candidates using Qikpro and Toxicity Estimation Software Tool (T.E.S.T). A total of 36 compounds were screened, of which nine displayed strong binding affinity and drug-likeness. Luteolin and chrysoeriol produced stronger results. These nine compounds were free of oral toxicity as evaluated by the Toxicity estimation software. Based on further in vitro, in vivo, and clinical effectiveness trials, these compounds may be used for the prevention or treatment as per the Indian system of traditional medicines.