Identification of Potential Phytochemical Inhibitors as Promising Therapeutics Against SARS-CoV-2 and Molecular Dynamics Simulation

Abstract

The high infectivity and mortality of novel coronavirus has caused a serious concern all over the world. Still, there is no specific drug or preventive medication to treat SARS-CoV-2 infection despite comprehensive analysis by the researchers. This study was designed to demonstrate the efficacy of some phyto-chemical compounds against SARS-CoV-2 by using both structure and ligand based virtual screening methods. A total of 33 plant metabolites were screened against SARS-CoV-2 main protease proteins (MPP), Nsp9 RNA binding protein, spike receptor binding domain and HR2 domain using a molecular docking approach. Results showed that three metabolites, i.e., Limonin, Isoflavone, and Coumadin conferred maximum binding affinity with all key proteins of SARS-CoV-2. For each viral protein, the critical binding sites and drug surface hotspots have been unraveled. ADME analysis indicated that none of the compounds have adverse effects that could decrease their drug-like properties. Moreover, toxicity pattern analysis also unmasked the non-toxic nature of the top drug candidates. The RMSD values of top ligandmacromolecule complexes were less than 2 Å, while RMSF values showed regular atomic fluctuations in the molecular dynamics study. Notably, most of the target class by top drug candidates belonged to enzyme groups (e.g. oxidoreductases, protease, Kinase). Results of drug similarity prediction revealed two approved structural analogs of Coumadin named Warfarin (DB00682) and Phenprocoumon (DB00946) from DrugBank. In addition, Isoformononetin an experimental drug analog of isoflavone could also be an option for the treatment of viral infections. For limonin there was no analog found in drugbank. The study can pave the way for the creation of effective SARS-CoV-2 medications and preventive measures. We highly recommend further in vivo trials for the experimental validation of our findings

Plant derived bioactive compounds as potential inhibitors of ZIKA virus: an in silico investigation

“…The binding affinity of 35 plant metabolites with different Zika virus proteins/protein domains (drug targets/macromolecules) were determined by using the PatchDock server (Supplimentary File 1). The PatchDock server complies geometry docking using the shape complementary principals and find out the best patch for the lingand including active sites of the macromolecules (Schneidman-Duhovny et al, 2005 and Banik et al, 2020). The clustering RMSD was set 4.0 and the macromolecule-small ligand type was utilized for docking purpose.…”

“…Recently, Pinocembrin a compound from honey has been suggested as a Zika virus replication inhibitor by experimental study (Lee et al, 2019) and used as a positive control for this present study. FireDock refinement tool utilized for refinement purpose of the docked complex (Mashiach et al, 2008 and Banik et al, 2020). The ligand bond complexes were visualized by Discovery Studio v3.1 and PyMOL v2.0 (Wang et al, 2015 and DeLano et al, 2002).…”

“…As a novel drug or vaccine development needs time while alternatively, medicinal plants could be used as early as possible in the manufacture of medicines. The importance of plants due to their medicinal benefit and therapeutic applications as ancient medicines has been documented by many scientific researchers (Azim et al, 2020; Koc et al, 2015; Banik et al, 2020 and Ahmed et al, 2019). Herbal bio-active compounds such as curcumin, a food supplement, have an antiviral activity against the Zika virus (Mounce et al, 2017).…”

Green solvents, plant metabolites, and COVID-19: Challenges and perspectives

“…Plants contain a wide range of viral protein inhibitors, which are usable in the treatment of viraltype diseases such as SARS. In general, plants can produce metabolites that exhibit inhibitory effects on enzymes, proteins, and virus propagation (Azim et al 2020a,b;Banik et al 2020;Bhuiyan et al 2020). The herbal immune system is a complex system that can detect and inactivate invading pathogens with various tools.…”

“…4668 bioactive species, and some of them have exhibited activity against coronavirus. These include 3-chymotrypsin-like protease, RNA-dependent RNA polymerase, papain-like protease, spike protein, angiotensin-converting enzyme II receptor or affect the life cycle of a coronavirus (Fuzimoto and Isidoro 2020;Banik et al 2020).…”