Surprisingly, we obtained good hits from our natural database which is good news since after observing their interaction and biotherapeutic functions, we might have achieved our COVID-19 inhibitory drugs. Products database.) Results (PDF). (Complete docking results from the Zinc Natural DDR1-IN-1 dihydrochloride Products database and the list of 129 drugs.) Extended data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Peer Review Summary by others. The transmission of this coronavirus occurs due to the binding of the CoV spike protein to the angiotensin converting enzyme 2 (ACE2) receptor present on the cell surface of the human host. The ACE2 receptor is present in the respiratory organs, kidneys, gastrointestinal tract (at high levels in the esophagus, colon, and small intestine, but low in the stomach), and testes. Virulence of this novel virus is due to the presence of main protease responsible for virus replication along with many major functions 6. Therefore, we have employed the main protease structure 6m03 as the target protein to identify the best inhibitory drugs for our study. SARS-CoV-2 (negatively stained) when observed under the electron micrograph was found to be spherical in shape with some pleiomorphic characteristic. The epithelial sections of human airway when observed, viruses were found in membrane bound vesicles in cytoplasm along with inclusion bodies. The virions appear similar to solar corona due to 9- to 12-nm distinctive spikes and the virions are 60 to 140 nm in diameter. Thus, it was established due to these morphological characteristics that this virus belongs to the Coronaviridae family along with its genome having more than 85% identity with a bat SARS-like CoV (bat-SL-CoVZC45, “type”:”entrez-nucleotide”,”attrs”:”text”:”MG772933.1″,”term_id”:”1369125417″,”term_text”:”MG772933.1″MG772933.1) genome as previously assessed via genome sequencing 6. SARS-Cov-2 initially infects lower airways, binds to DDR1-IN-1 dihydrochloride ACE2 receptor on cells activating immune cells, thus, inducing the secretion of inflammatory cytokines and chemokines in human pulmonary system 4. Most COVID-19 patients exhibit flu-like symptoms within a span of two weeks from the exposure to the virus whereas there have been a majority rise in the asymptomatic COVID-19 patients. In this work, we have performed high throughput virtual screening since it is the fastest approach in finding the probable drug against the target. High-throughput virtual screening (HTVS) of two databases DDR1-IN-1 dihydrochloride was carried out via PyRx (Python prescription) software, which uses dock, Vina and Autodock as the docking tool. Autodock itself uses MGLTools comprising of computer aided drug discovery (CADD) pipeline for high throughput virtual screening of large databases for probable hits as target drugs. HTVS enables docking of multiple ligands on a single protein. PyRx is a freely available HTVS software. Docking results are based on the identification of pose visually and quantitatively using a scoring algorithm. Docking calculates the free binding energy (?G) between the ligands and the protein. The free DDR1-IN-1 dihydrochloride binding energy, thus calculated, is fundamental to the formation of complex systems in biochemistry and molecular biology. Lower free binding energy corresponds to a more favorable ligand binding affinity between a receptor and a ligand 7. Methods Molecular docking Molecular docking is a bioinformatics method Rabbit Polyclonal to Ezrin (phospho-Tyr146) that allows predicting the orientation of a molecule, when it is bounded to another molecule 8, 9. There are two main approaches for molecular docking. The first approach describes the protein and the ligand as complementary surfaces 10. The second approach simulates the docking process calculating the ligand protein interaction based on the free binding energy ?G 11. Molecule selection Selection of database and the COVID-19 main protease structure In this study, we have docked the X-ray crystal structure of main COVID protease protein (PDB ID: 6M03, resolution: 2 ?) with 129 molecules obtained from DrugBank and 992 molecules from the Zinc Natural Product database. The list of 129 molecules are provided along with the link for Zinc natural database in the IDpneumonia and malaria. Tetrandrine is in the experimental stage for anticancer, antimalarial, antiparasitic category. Eprinomectin and doramectin are veterinary antiparasitic drugs. Many of the natural compounds identified have medicinal properties. Taraxerone has allelopathic and antifungal effect 20, Morusin has anti-oxidant and anticancer properties 21, RA VII compound is an antitumor agent 22, and neoruscogenin is used against chronic venous disorders 23. Justicidin D exhibits anti-inflammatory properties 24, Licoricidin is an antimetastatic molecule 25.