Abstract
The pandemic, COVID-19, has spread worldwide and affected millions of people. There is an urgent need, therefore, to find a proper treatment for the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent. This paper focuses on identifying inhibitors that target SARS-CoV-2 proteases, PL PRO and 3CL PRO , which control the duplication and manages the life cycle of SARS-CoV-2. We have carried out detailed in silico Virtual high-throughput screening using Food and Drug Administration (FDA) approved drugs from the Zinc database, COVID-19 clinical trial compounds from Pubchem database, Natural compounds from Natural Product Activity and Species Source (NPASS) database and Maybridge database against PL PRO and 3CL PRO proteases. After thoroughly analyzing the screening results, we found five compounds, Bemcentinib, Pacritinib, Ergotamine, MFCD00832476, and MFCD02180753 inhibit PL PRO and six compounds, Bemcentinib, Clofazimine, Abivertinib, Dasabuvir, MFCD00832476, Leuconicine F inhibit the 3CL PRO . These compounds are stable within the protease proteins’ active sites at 20ns MD simulation. The stability is revealed by hydrogen bond formations, hydrophobic interactions, and salt bridge interactions. Our study results also reveal that the selected five compounds against PL PRO and the six compounds against 3CL PRO bind to their active sites with good binding free energy. These compounds that inhibit the activity of PL PRO and 3CL PRO may, therefore, be used for treating COVID-19 infection.
Keywords: 3CL(PRO); COVID-19; Drug repositioning; PL(PRO); SARS-CoV-2.
【저자키워드】 COVID-19, SARS-CoV-2, drug repositioning, 3CL(pro), PL(pro), 【초록키워드】 Treatment, SARS-CoV-2, Zinc, clinical trial, pandemic, Infection, severe acute respiratory syndrome coronavirus-2, drug, 3CL pro, protease, in silico, severe acute respiratory syndrome Coronavirus, FDA, binding free energy, inhibitors, database, ZINC database, MD simulation, approved drugs, free energy, Novel coronavirus, activity, Food and Drug Administration, Spread, Protein, stability, COVID-19 infection, Proteases, respiratory, inhibitor, interactions, 3CL, compounds, food, Hydrogen bond, life cycle, causative agent, bemcentinib, active site, hydrogen, Clofazimine, approved drug, Pacritinib, natural, acute respiratory syndrome, Ergotamine, Compound, product, Drug administration, hydrophobic, these compounds, treating COVID-19, hydrophobic interactions, PubChem database, Abivertinib, duplication, FIVE, dasabuvir, Salt Bridge, selected, affected, carried, inhibit, Specy, Source, 【제목키워드】 SARS-CoV-2, protease, inhibitor, 3CL, Potential,