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Safe, effective, and readily available COVID-19 therapeutics are urgently needed to prepare for future coronavirus pandemics. To help identify new antiviral agents, the present study focused on natural products in the extracts of Holy Basil, <jats:italic>Ocimum tenuiflorum<\/jats:italic> L., which show potential inhibitory effects against the SARS-CoV-2 main protease (M<jats:sup>pro<\/jats:sup>). Bioassay-guided isolation of the MeOH extracts of <jats:italic>O. tenuiflorum<\/jats:italic> led to the identification of a sulfur-containing glyceroglycolipid, sulfoquinovosyl diacylglycerol (SQDG: <jats:bold>1<\/jats:bold>), as a potent M<jats:sup>pro<\/jats:sup> inhibitor that effectively inhibited M<jats:sup>pro<\/jats:sup> activity (IC<jats:sub>50<\/jats:sub>: 0.42 \u00b5M). SQDG (<jats:bold>1<\/jats:bold>) also markedly suppressed SARS-CoV-2 replication (EC<jats:sub>50<\/jats:sub>, 51.2 \u00b5M) <jats:italic>in vitro<\/jats:italic> while displaying no cytotoxicity (CC<jats:sub>50<\/jats:sub> &gt; 100 \u00b5M). Further inhibition kinetic studies and docking simulations clearly demonstrated that SQDG strongly inhibited SARS-CoV-2 M<jats:sup>pro<\/jats:sup>\n            <jats:italic>in<\/jats:italic> a competitive and mixed-inhibition manner. These findings highlight SQDG as a promising lead compound for COVID-19 therapy and emphasize the need to explore new drugs from natural sources.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical Abstract<\/jats:bold>\n          <\/jats:p>","DOI":"10.1007\/s11418-024-01855-6","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T15:08:04Z","timestamp":1732547284000},"page":"122-133","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sulfoquinovosyl diacylglycerol, a component of Holy Basil Ocimum tenuiflorum, inhibits the activity of the SARS-CoV-2 main protease and viral replication in vitro"],"prefix":"10.1007","volume":"79","author":[{"given":"Hinako","family":"Koze","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Sudoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoaki","family":"Onitsuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Okamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumito","family":"Tani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukako","family":"Miyata-Yabuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikako","family":"Shirouzu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Baba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7631-7974","authenticated-orcid":false,"given":"Toshiyuki","family":"Hamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"key":"1855_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2020.106137","volume":"56","author":"L Wang","year":"2020","unstructured":"Wang L, Wang Y, Ye D, Liu Q (2020) Erratum to \u201cA review of the 2019 Novel Coronavirus (COVID-19) based on current evidence\u201d [International Journal of Antimicrobial Agents 55\/6 (2020) 105948]. 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