Phytocompounds of Rheum emodi, Thymus serpyllum, and Artemisia annua Inhibit Spike Protein of SARS-CoV-2 Binding to ACE2 Receptor: In Silico Approach

Abstract

, the disease caused by SARS-CoV-2, has been declared as a global pandemic. Traditional medicinal plants have long history to treat viral infections. Our in silico approach suggested that unique phytocompounds such as emodin, thymol and carvacrol, and artemisinin could physically bind SARS-CoV-2 spike glycoproteins (6VXX and 6VYB), SARS-CoV-2 B.1.351 South Africa variant of Spike glycoprotein (7NXA), and even with ACE2 and prevent the SARS-CoV-2 binding to the host ACE2, TMPRSS2 and neutrapilin-1 receptors. Since Chloroquine has been looked as potential therapy against COVID-19, we also compared the binding of chloroquine and artemisinin for its interaction with spike proteins (6VXX, 6VYB) and its variant 7NXA, respectively. Molecular docking study of phytocompounds and SARS-CoV-2 spike protein was performed by using AutoDock/Vina software. Molecular dynamics (MD) simulation was performed for 50ns. Among all the phytocompounds, molecular docking studies revealed lowest binding energy of artemisinin with 6VXX and 6VYB, with E total −10.5 KJ mol −1 and −10.3 KJ mol −1 respectively. Emodin showed the best binding affinity with 6VYB with E total −8.8 KJ mol −1 and SARS-CoV-2 B.1.351 variant (7NXA) with binding energy of −6.4KJ mol −1 . Emodin showed best interactions with TMPRSS 2 and ACE2 with E total of −7.1 and −7.3 KJ mol −1 respectively, whereas artemisinin interacts with TMPRSS 2 and ACE2 with E total of −6.9 and −7.4 KJ mol −1 respectively. All the phytocompounds were non-toxic and non-carcinogenic. MD simulation showed that artemisinin has more stable interaction with 6VYB as compared to 6VXX, and hence proposed as potential phytochemical to prevent SARS-CoV-2 interaction with ACE-2 receptor.

Computational screening of camostat and related compounds against human TMPRSS2: A potential treatment of COVID-19

“…There were several other residues, namely K342, C437, Q438, D440, T459, S460, G462, G464, A466, P471, and G472, involved in van der Waals interaction with most of the compounds. Previous studies have well documented the contributory role of these active site residues ( Rolta et al, 2021 , Tateyama-Makino et al, 2021 ).

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Phytocompounds from Himalayan Medicinal Plants as Potential Drugs to Treat Multidrug-Resistant Salmonella typhimurium: An In Silico Approach

“…Rolta et al [87] studied the antibacterial and antifungal activities of phytocompounds of Rheum emodin (emodin, rhein-13c6, and chrysophenodimethy ether) by molecular docking and MD simulations and found that phytocompounds of R. emodin exhibited the best interaction with bacterial and fungal targets. Similarly, Rolta et al [71] studied the interactions of phytocompounds with the N-protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 2020, and reported that emodin, aloe-emodin, anthrarufin, alizarine, and dantron phytocompounds efficiently inhibit SARS-CoV-2 N-protein. Salaria et al [88] studied the in vitro and in silico antibacterial and antifungal activities of essential oil, thymol derived from Thymus serpyllum, and validated the docking results via MD simulations.…”

“…Absorption, distribution, metabolism, excretion, and toxicity (ADMET) screening was performed to evaluate the absorption, toxicity, and drug-likeness properties of the selected phytocompounds. The 3-D structures of 11 phytocompounds (asiaticoside, betasitosterol, bryophyllin A, madecassoside, Mahanimbine, Pennogenin, Rutin, Solasonine, Solamargine, Withaferin A, and Withanone) were saved in smiles format and uploaded on the SWISSADME (http://www.swissadme.ch/) (Molecular Modeling Group of the SIB (Swiss Institute of Bioinformatics) and PROTOX-II (https://tox-new.charite.de/protox_II/) web servers (Charite University of Medicine, Institute for Physiology, Structural Bioinformatics Group, Berlin, Germany) [69][70][71][72] for ADMET screening. SWISSADME is an online tool used to predict ADME and pharmacokinetic and physicochemical features of a molecule, which are the main determinants for clinical trials.…”

Screening of Natural Products Inhibitors of SARS-CoV-2 Entry

“…In addition, bioinformatics studies such as molecular docking have identified natural products with potential antiviral activity against SARS-CoV-2 by blocking the interaction between the spike protein and the ACE2 receptor. Some of the compounds identified by this strategy are artemisinin and gamma mangostin [ 12 , 13 ]. It is important to note that experimental validation of these data based on bioinformatics models is necessary.…”