ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese medicine sappanwood is primarily sourced from the dried heartwood of the medicinal plant Caesalpinia sappan Linn., which has been found with a variety of valuable properties including anti-inflammatory, anti-oxidant, and anti-viral effects. Preliminary investigations have demonstrated that sappanwood showed strong anti-SARS-CoV-2 M AIM OF THE STUDY: This study aims to uncover the naturally occurring covalent inhibitors of SARS-CoV-2 M MATERIALS AND METHODS: The proteolytic activity of SARS-CoV-2 M RESULTS: SWE was found with strong anti-M CONCLUSIONS: The naturally occurring covalent inhibitors of SARS-CoV-2 M