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The severe form of respiratory disease (COVID-19), caused by SARS-COV-2 virus, has evolved into a pandemic is the defining global health crisis of our time and greatest challenge we have faced since second World War. Hence, the current situation demands an immediate need to explore all the possible therapeutic strategies that can be control spread of the diseases. We identified potent COVID-19 Mpro inhibitors based on molecular docking studies on 24 known antiviral natural compounds, which are from medicinal plants and marine sponges. The results revealed that 15 potential COVID-19 main protease inhibitors have been identified among the 24 natural compounds of plants and marine origin. The result further revealed that the selected natural products that has lower free binding energy is Halituline (-8.41 Kcal/mol). As these active compounds were extensively validated by molecular docking, the chance that at least few of these compounds could be bioactive is excellent.