key: cord-0831791-wbz8a934 authors: Mhatre, Susmit; Naik, Shivraj; Patravale, Vandana title: A Molecular Docking Study of EGCG and Theaflavin Digallate with the Druggable Targets of SARS-CoV-2 date: 2020-11-23 journal: Comput Biol Med DOI: 10.1016/j.compbiomed.2020.104137 sha: 6c251a79cd0c7c0fbfa8d05dfa23d3181ac3d824 doc_id: 831791 cord_uid: wbz8a934 BACKGROUND: COVID-19 is an infectious disease caused by a novel positive-sense single-stranded RNA coronavirus called as SARS-CoV-2. This viral disease is known to infect the respiratory system, eventually leading to pneumonia. Crystallographic studies of the viral structure reveal its mechanism of infection as well as active binding sites and the druggable targets as scope for treatment of COVID-19. HYPOTHESIS: The role of tea polyphenols in prophylaxis and treatment of COVID-19 was established in this study. STUDY DESIGN: Molecular docking interactions of tea polyphenols with some of the possible binding sites of SARS-CoV-2 were performed. MATERIALS AND METHODS: From various studies on the SARS-CoV-2 reported in the literature, we chose possible drug targets (Chymotrypsin-like protease, RNA dependant RNA polymerase, Papain like protease, Spike RBD and ACE2 receptor with spike RBD) which are vital proteins. These receptors were docked against two tea polyphenols, Epigallocatechin gallate (EGCG) from green tea and Theaflavin digallate (TF3) from black tea. These polyphenols have been previously reviewed for their antiviral activities, especially against single-stranded RNA viruses. Two antiviral drugs, Remdesivir and Favipiravir were studied for comparative docking results. RESULTS: A comparative study of docking scores and the type of interactions of EGCG, TF3 with the possible targets of COVID-19 showed that the tea polyphenols had good docking scores with significant in-silico activity. CONCLUSION: These results can provide a lead in exploring both the tea polyphenols in prophylaxis as well as treatment of COVID-19. The crystallographic structure of SARS-CoV-2 reveals that the virus is a positive-sense studies of tea polyphenols on the main protease of SARS-CoV-2 and discussed their potential 119 as inhibitors of 3CLpro [13] . The catechins found in green tea are catechin, gallocatechin 120 (GC), epicatechin (EC), epicatechin-3-gallate (ECG), epigallocatechin (EGC) and 121 epigallocatechin-3-gallate (EGCG). Out of these, EGCG is found in the highest quantity in 122 green tea, and also researched extensively as compared to the other catechins owing to its 123 antiviral properties [14] . The theaflavins found in black tea are theaflavin (TF1), theaflavin-3-124 gallate (TF2a), theaflavin-3'-gallate (TF2b) and theaflavin-3,3-digallate (TF3). TF3 has 125 particularly shown better antiviral activity than the other theaflavins [15] . In this study, we 126 analysed interactions of two prime phytoconstituents present in tea, EGCG from green tea 127 and TF2b from black tea with known binding sites of SARS-CoV-2 to anticipate the probable 128 use of these polyphenols as a treatment method in COVID-19. binding modes were generated. Out of these modes, the binding mode with the best docking 191 score was saved as a .pdb file and was used for further evaluation. This ligand-receptor 192 complex was then minimized again using the same parameters used to prepare the receptor. The interactions formed between the receptors and the ligands were visualized using The pharmacokinetic properties were evaluated using the Swiss ADME and the 219 pkCSM web server [30, 31] . The entire methodology is summarized in figure 3 . The amino acid residues composition of the binding sites and their grid coordinates for 225 the receptors is summarized in Table 1 and Favipiravir as observed from the interaction diagram in figure 3 . The polyphenols also showed a considerable binding affinity towards complex formed 2 Spike RBD EGCG GLY92, TYR32, TYR453, TYR495, GLU406, GLN409, THR415, TYR58, ASP95, TYR33, ASP97, TYR52 ARG403, LYS417, VAL50, TRP47, GLY416, SER94 TF3 SER35, LEU455, TYR33. TYR52, TYR453, VAL98, TYR32, GLY92, GLU406, SER93, ASP405, GLN409, GLY416, ARG408, LYS64, TYR58, ALA60, TRP47 LYS417, ARG403, VAL50 RdRp EGCG THR806, LEU805, TYR826, TYR606, ASP608 PRO612, LYS603 TF3 THR604, PRO612, LEU805, TYR606, GLU610, LYS751, ASP608 -Remdesivir TYR828, PRO612, The physicochemical properties of these molecules were studied and summarized in table 4. Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures SwissADME: a free web tool to evaluate 495 pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small 496 molecules Understanding the Functional Roles of 498 Amino Acid Residues in Enzyme Catalysis Potential anti-viral activity of approved repurposed 502 drug against main protease of SARS-CoV-2: an in silico based approach Silico Exploration of the Molecular Mechanism of 506 Clinically Oriented Drugs for Possibly Inhibiting SARS-CoV-2's Main Protease Drug repurposing for 509 coronavirus (COVID-19): in silico screening of known drugs against coronavirus 3CL 510 hydrolase and protease enzymes Ongoing Clinical Trials for the Management of the 513 COVID-19 Pandemic Compounds Derived from Epigallocatechin-3-Gallate (EGCG) as a Novel 516 Approach to the Prevention of Viral Infections A proprietary 519 topical preparation containing EGCG-stearate and glycerin with inhibitory effects on 520 herpes simplex virus: case study