The current emergency due to the worldwide spread of the COVID-19 caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a great concern for global public health. Already in the past, the outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle Eastern respiratory syndrome (MERS) in 2012 demonstrates the potential of coronaviruses to cross-species borders and further underlines the importance of identifying new-targeted drugs. An ideal antiviral agent should target essential proteins involved in the lifecycle of SARS-CoV. Currently, some HIV protease inhibitors (i.e., Lopinavir) are proposed for the treatment of COVID-19, although their effectiveness has not yet been assessed. The main protease (M pro ) provides a highly validated pharmacological target for the discovery and design of inhibitors. We identified potent M pro inhibitors employing computational techniques that entail the screening of a Marine Natural Product (MNP) library. MNP library was screened by a hyphenated pharmacophore model, and molecular docking approaches. Molecular dynamics and re-docking further confirmed the results obtained by structure-based techniques and allowed this study to highlight some crucial aspects. Seventeen potential SARS-CoV-2 M pro inhibitors have been identified among the natural substances of marine origin. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds could be bioactive is excellent.
【저자키워드】 COVID-19, SARS-CoV-2, Virtual screening, docking, marine natural product, 【초록키워드】 Treatment, coronavirus, Antiviral, SARS-CoV, Lopinavir, drugs, molecular docking, molecular dynamics, protease, MERS, HIV protease inhibitor, inhibitors, Spread, Protein, outbreak, Effectiveness, molecular, inhibitor, Consensus, natural, acute respiratory syndrome, global public health, approaches, M pro, syndrome, product, lifecycle, middle, pharmacological target, approach, likelihood, highlight, caused, involved, screened, provide, coronavirus, these compound, MNP, 【제목키워드】 Screening, modeling, natural, library,