{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:54:09Z","timestamp":1785405249579,"version":"3.56.0"},"reference-count":67,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Program of Fundamental Research of the Ministry of Education and Training","award":["B2025-SPS-01"],"award-info":[{"award-number":["B2025-SPS-01"]}]},{"award":["B2025-SPS-01"],"award-info":[{"award-number":["B2025-SPS-01"]}],"id":[{"id":"https:\/\/ror.org\/00drv3378","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Vitex rotundifolia is a medicinal plant rich in terpenoids and flavonoids, whereas the liverwort Ptychanthus striatus represents an underexplored bryophyte source of specialized metabolites. In this study, a bioassay-guided phytochemical investigation of Vietnamese V. rotundifolia leaves and P. striatus was conducted to identify natural inhibitors of SARS-CoV-2 main protease (Mpro). The crude methanol extracts and selected fractions showed inhibitory activity against SARS-CoV-2 Mpro, thereby guiding subsequent chromatographic separation. Thirteen compounds, including diterpenoids, lupane-type triterpenoids, and flavonoids, were isolated from V. rotundifolia, while ten terpenoid, phenolic, bibenzyl, and bisbibenzyl-type metabolites were obtained from P. striatus. Most isolated compounds are reported from these species for the first time, and compound P8 from P. striatus is described as a new natural product. All isolated compounds were evaluated for their inhibitory activity against SARS-CoV-2 Mpro. Among them, chrysoplenol D was the most potent inhibitor, with an IC50 value of 0.08 \u00b1 0.01 \u00b5M, followed by selected phenolic\/bibenzyl-type metabolites from P. striatus and other flavonoid derivatives from V. rotundifolia. Most diterpenoids showed weak or negligible inhibition. Molecular docking studies supported the experimental results by showing that representative active compounds could bind within the catalytic pocket of SARS-CoV-2 Mpro and interact with key residues, including His41, Gly143, and Cys145. These findings expand the phytochemical knowledge of Vietnamese V. rotundifolia and P. striatus and highlight chrysoplenol D and related flavonoid or bibenzyl-type natural products as promising scaffolds for further development of SARS-CoV-2 Mpro inhibitors.<\/jats:p>","DOI":"10.3390\/molecules31122009","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T16:25:16Z","timestamp":1780935916000},"page":"2009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioassay-Guided Phytochemical Investigation of Vietnamese Vitex rotundifolia Leaves and the Liverwort Ptychanthus striatus as Sources of SARS-CoV-2 Main Protease Inhibitors"],"prefix":"10.3390","volume":"31","author":[{"given":"Huy Truong","family":"Nguyen","sequence":"first","affiliation":[{"name":"Research Group in Pharmaceutical and Biomedical Sciences, Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi-Minh Dinh","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Biology, Ho Chi Minh City University of Education, 280 An Duong Vuong Street, Cho Quan Ward, Ho Chi Minh City 748342, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9891-4326","authenticated-orcid":false,"given":"Thuc-Huy","family":"Duong","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ho Chi Minh City University of Education, 280 An Duong Vuong Street, Cho Quan Ward, Ho Chi Minh City 748342, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trong-Hieu","family":"Bui","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ho Chi Minh City University of Education, 280 An Duong Vuong Street, Cho Quan Ward, Ho Chi Minh City 748342, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen-Kim-Tuyen","family":"Pham","sequence":"additional","affiliation":[{"name":"Faculty of Engineering and Technology, Saigon University, Cho Quan Ward, Ho Chi Minh City 748342, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai-Dang-Truong","family":"Pham","sequence":"additional","affiliation":[{"name":"Institute of Advanced Technology, Vietnam Academy of Science and Technology, Hanoi 100000, Vietnam"},{"name":"Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoang-Truc-Nguyen","family":"Phan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ho Chi Minh City University of Education, 280 An Duong Vuong Street, Cho Quan Ward, Ho Chi Minh City 748342, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinh-Tri","family":"Mai","sequence":"additional","affiliation":[{"name":"Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warudee","family":"Pathummanee","sequence":"additional","affiliation":[{"name":"Department of Fundamental Science and Physical Education, Faculty of Science at Sriracha, Kasetsart University, Chonburi 20230, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5157-4000","authenticated-orcid":false,"given":"Duc-Dung","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ho Chi Minh City University of Education, 280 An Duong Vuong Street, Cho Quan Ward, Ho Chi Minh City 748342, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1431-3668","authenticated-orcid":false,"given":"Tongsai","family":"Jamnongkan","sequence":"additional","affiliation":[{"name":"Department of Fundamental Science and Physical Education, Faculty of Science at Sriracha, Kasetsart University, Chonburi 20230, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/s41564-020-0695-z","article-title":"The Species Severe Acute Respiratory Syndrome-Related Coronavirus: Classifying 2019-nCoV and Naming It SARS-CoV-2","volume":"5","author":"Gorbalenya","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41579-020-00468-6","article-title":"Coronavirus Biology and Replication: Implications for SARS-CoV-2","volume":"19","author":"Kratzel","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"31","DOI":"10.56782\/pps.292","article-title":"BioNTech\/Pfizer (BNT162b2) COVID-19 mRNA Vaccine: Manufacturing, Immunogenicity, Efficacy and Safety","volume":"23","author":"Alkhalil","year":"2025","journal-title":"Prospect. Pharm. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41586-020-2223-y","article-title":"Structure of Mpro from SARS-CoV-2 and Discovery of Its Inhibitors","volume":"582","author":"Jin","year":"2020","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"127377","DOI":"10.1016\/j.bmcl.2020.127377","article-title":"The SARS-CoV-2 Main Protease as Drug Target","volume":"30","author":"Ullrich","year":"2020","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1039\/D3MD00493G","article-title":"On the Origins of SARS-CoV-2 Main Protease Inhibitors","volume":"15","author":"Janin","year":"2024","journal-title":"RSC Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1007\/s40265-024-02039-y","article-title":"Ensitrelvir Fumaric Acid: First Approval","volume":"84","author":"Syed","year":"2024","journal-title":"Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"eadi0979","DOI":"10.1126\/scitranslmed.adi0979","article-title":"An Orally Bioavailable SARS-CoV-2 Main Protease Inhibitor Exhibits Improved Affinity and Reduced Sensitivity to Mutations","volume":"16","author":"Westberg","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12197","DOI":"10.1038\/s41598-022-15930-z","article-title":"Hepatitis C Virus NS3\/4A Inhibitors and Other Drug-like Compounds as Covalent Binders of SARS-CoV-2 Main Protease","volume":"12","author":"Andi","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Diogo, M.A., Cabral, A.G.T., and De Oliveira, R.B. (2024). Advances in the Search for SARS-CoV-2 Mpro and PLpro Inhibitors. Pathogens, 13.","DOI":"10.3390\/pathogens13100825"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"44624","DOI":"10.1021\/acsomega.4c07148","article-title":"Inhibitory Effects of Mangifera Indica Secondary Metabolites and Their Synthetic Derivatives against SARS-CoV-2 Mpro and NS2B\/NS3 (ZIKV and DENV-2)","volume":"9","author":"Souza","year":"2024","journal-title":"ACS Omega"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3110","DOI":"10.1080\/14786419.2021.1935933","article-title":"Virtual Screening, ADMET Profiling, PASS Prediction, and Bioactivity Studies of Potential Inhibitory Roles of Alkaloids, Phytosterols, and Flavonoids against COVID-19 Main Protease (Mpro)","volume":"36","author":"Adedotun","year":"2022","journal-title":"Nat. Prod. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1002\/ptr.6998","article-title":"In Silico and In Vitro Evaluation of Kaempferol as a Potential Inhibitor of the SARS-CoV-2 Main Protease (3CLpro)","volume":"35","author":"Khan","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e29208","DOI":"10.1002\/jmv.29208","article-title":"Discovery of the Covalent SARS-CoV-2 Mpro Inhibitors from Antiviral Herbs via Integrating Target-based High-throughput Screening and Chemoproteomic Approaches","volume":"95","author":"Zhang","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"204","DOI":"10.22159\/ajpcr.2020.v13i5.37909","article-title":"\u03b2-Sitosterol: Isolation from Muntingia Calabura Linn. Bark Extract, Structural Elucidation, and Molecular Docking Studies as Potential Inhibitor of SARS-CoV-2 Mpro (COVID-19)","volume":"13","author":"Chaudhari","year":"2020","journal-title":"Asian J. Pharm. Clin. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4234","DOI":"10.1080\/07391102.2023.2220040","article-title":"Searching Possible SARS-CoV-2 Main Protease Inhibitors in Constituents from Herbal Medicines Using In Silico Studies","volume":"42","author":"Rasul","year":"2024","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"533","DOI":"10.3897\/pharmacia.68.e68432","article-title":"Molecular Docking of Secondary Metabolites from Indonesian Marine and Terrestrial Organisms Targeting SARS-CoV-2 ACE-2, M pro, and PL pro Receptors","volume":"68","author":"Syahputra","year":"2021","journal-title":"Pharmacia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e00907","DOI":"10.1002\/cbdv.202500907","article-title":"Natural Inhibitors Against Severe Acute Respiratory Syndrome Coronavirus 2 Main Protease From Three Vietnamese Bryophytes","volume":"22","author":"Le","year":"2025","journal-title":"Chem. Biodivers."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1021\/acs.jnatprod.6b01046","article-title":"Chemical Constituents of Bryophytes: Structures and Biological Activity","volume":"81","author":"Asakawa","year":"2018","journal-title":"J. Nat. Prod."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/S0031-9422(99)00227-7","article-title":"Ptychantols A\u2013C, Macrocyclic Bis(Bibenzyls), Possessing a Trans-Stilbene Structure from the Liverwort Ptychanthus striatus","volume":"52","author":"Hashimoto","year":"1999","journal-title":"Phytochemistry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5307","DOI":"10.1016\/S0040-4039(01)92488-8","article-title":"Ptychanolide, a Sesquiterpenoid with a New Type Skeleton from the Liverwort Ptychanthus striatus (Lehm. et Lindenb.) Nees","volume":"22","author":"Takeda","year":"1981","journal-title":"Tetrahedron Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/jccs.200100039","article-title":"Ptychantins from the Liverwort Ptychanthus striatus","volume":"48","author":"Wu","year":"2001","journal-title":"J. Chin. Chem. Soc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1080\/10286020.2015.1011140","article-title":"Polyacetylated Labdane-Type Diterpenoids, Ptychantins P\u2013R from Chinese Liverwort Ptychanthus striatus","volume":"17","author":"Wu","year":"2015","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_24","first-page":"890","article-title":"Evaluation of Anti-Diabetic, Antioxidant Activity and Phytochemical Constituents of Liverworts of Eastern Himalaya","volume":"7","author":"Mukhia","year":"2015","journal-title":"J. Chem. Pharm. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s11418-011-0587-x","article-title":"In Vitro Antitrypanosomal Activity of Bis(Bibenzyls)s and Bibenzyls from Liverworts against Trypanosoma Brucei","volume":"66","author":"Otoguro","year":"2012","journal-title":"J. Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sen, K., Khan, M.I., Paul, R., Ghoshal, U., and Asakawa, Y. (2023). Recent Advances in the Phytochemistry of Bryophytes: Distribution, Structures and Biological Activity of Bibenzyl and Bisbibenzyl Compounds. Plants, 12.","DOI":"10.3390\/plants12244173"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"39","DOI":"10.7872\/cryb.v33.iss1.2012.039","article-title":"Lejeuneaceae Subfamily Ptychanthoideae (Marchantiophyta) in Thailand","volume":"33","author":"Kornochalert","year":"2012","journal-title":"Cryptogam. Bryol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"188","DOI":"10.4103\/0973-7847.120522","article-title":"The Genus Vitex: A Review","volume":"7","author":"Rani","year":"2013","journal-title":"Pharmacogn. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11","DOI":"10.53388\/TMR20201128209","article-title":"The Coastal Medicinal Plant Vitex rotundifolia: A Mini-Review on Its Bioactive Compounds and Pharmacological Activity","volume":"6","author":"Husna","year":"2021","journal-title":"Tradit. Med. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1016\/S0031-9422(99)00405-7","article-title":"Aryl Naphthalenes Norlignans from Vitex rotundifolia","volume":"52","author":"Kawazoe","year":"1999","journal-title":"Phytochemistry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.canlet.2004.01.012","article-title":"G2-M Arrest and Antimitotic Activity Mediated by Casticin, a Flavonoid Isolated from Viticis Fructus (Vitex rotundifolia Linne Fil.)","volume":"208","author":"Kobayakawa","year":"2004","journal-title":"Cancer Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/0031-9422(88)83153-4","article-title":"Iridoid and Phenolic Glucoside from Vitex rotundifolia","volume":"27","author":"Kouno","year":"1988","journal-title":"Phytochemistry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0031-9422(97)00863-7","article-title":"A Labdane Diterpene Glycoside from Fruit of Vitex rotundifolia","volume":"48","author":"Ono","year":"1998","journal-title":"Phytochemistry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1021\/np990204x","article-title":"Diterpenes from the Fruits of Vitex rotundifolia","volume":"62","author":"Ono","year":"1999","journal-title":"J. Nat. Prod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1248\/cpb.49.82","article-title":"Ten New Labdane-Type Diterpenes from the Fruit of Vitex rotundifolia","volume":"49","author":"Ono","year":"2001","journal-title":"Chem. Pharm. Bull."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1021\/np0105331","article-title":"New Diterpenes and Norditerpenes from the Fruits of Vitex rotundifolia","volume":"65","author":"Ono","year":"2002","journal-title":"J. Nat. Prod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1515\/znc-2004-7-810","article-title":"Phenolic Compounds and Flavonoids as Plant Growth Regulators from Fruit and Leaf of Vitex rotundifolia","volume":"59","author":"Yoshioka","year":"2004","journal-title":"Z. Naturforschung C"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"585338","DOI":"10.2147\/DDDT.S585338","article-title":"Phytochemical and Anti-Ischemic Stroke Properties from the Vitex L. Genus","volume":"20","author":"Xie","year":"2026","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100608","DOI":"10.1016\/j.prmcm.2025.100608","article-title":"Investigation of the Main Active Ingredients of Vitex rotundifolia L.f and Assessment of Their Contribution to the Activity of This Species","volume":"15","author":"Lam","year":"2025","journal-title":"Pharmacol. Res. Mod. Chin. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.fitote.2017.06.006","article-title":"Diterpenoids with Diverse Scaffolds from Vitex trifolia as Potential Topoisomerase I Inhibitor","volume":"120","author":"Luo","year":"2017","journal-title":"Fitoterapia"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5419","DOI":"10.1016\/S0040-4039(03)01315-7","article-title":"Synthesis and Absolute Configuration of (\u2212)-Chrysolic Acid and (+)-Isofregenedol","volume":"44","author":"Marcos","year":"2003","journal-title":"Tetrahedron Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1039\/C7SC03842A","article-title":"Caged Circular siRNAs for Photomodulation of Gene Expression in Cells and Mice","volume":"9","author":"Zhang","year":"2018","journal-title":"Chem. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1021\/np010223i","article-title":"Sesqui- and Diterpenoids from the Japanese Liverwort Jungermannia i Nfusca","volume":"64","author":"Nagashima","year":"2001","journal-title":"J. Nat. Prod."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"198","DOI":"10.22159\/ijap.2021v13i2.40372","article-title":"The Anticholesterol Activity of Betulinic Acid and Stigmasterol Isolated from the Leaves of Sungkai (Paronema Canescens Jack)","volume":"13","author":"Muharni","year":"2021","journal-title":"Int. J. Appl. Pharm."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e202300390","DOI":"10.1002\/cbdv.202300390","article-title":"New Halogenated Flavonoids from Adenosma bracteosum and Vitex Negundo and Their \u03b1-Glucosidase Inhibition","volume":"20","author":"Nguyen","year":"2023","journal-title":"Chem. Biodivers."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/S0031-9422(00)90359-5","article-title":"Sphenolobane and Fusicoccane Diterpenoids from the Liverwort Anastrophyllum auritum","volume":"37","author":"Zapp","year":"1994","journal-title":"Phytochemistry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1021\/np100472d","article-title":"Bioactive Sesqui- and Diterpenoids from the Argentine Liverwort Porella chilensis","volume":"74","author":"Gilabert","year":"2011","journal-title":"J. Nat. Prod."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.3109\/13880209.2014.898078","article-title":"Beta-Amyrin and Alpha-Amyrin Acetate Isolated from the Stem Bark of Alstonia Boonei Display Profound Anti-Inflammatory Activity","volume":"52","author":"Okoye","year":"2014","journal-title":"Pharm. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ymben.2014.12.001","article-title":"Reconstructing the Chemical Diversity of Labdane-Type Diterpene Biosynthesis in Yeast","volume":"28","author":"Ignea","year":"2015","journal-title":"Metab. Eng."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"131524","DOI":"10.1016\/j.tet.2020.131524","article-title":"Asymmetric Total Synthesis of Dihydroisocoumarins: 6-Methoxymellein, Kigelin and Fusarentin 6, 7 Dimethyl Ether by Employing Proline Catalysed Asymmetric \u03b1-Aminoxylation","volume":"76","author":"Markad","year":"2020","journal-title":"Tetrahedron"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Xu, Q., Qiao, Y., Zhang, Z., Deng, Y., Chen, T., Tao, L., Xu, Q., Liu, J., Sun, W., and Ye, Y. (2021). New Polyketides With Anti-Inflammatory Activity From the Fungus Aspergillus rugulosa. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.700573"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0031-9422(00)80821-3","article-title":"The Isolation of Methyl \u03b2-Orsellinate from Stereocaulon alpinum and Comments on the Isolation of 4,6-Dihydroxy-2-Methoxy-3-Methylacetophenone from Stereocaulon Species","volume":"24","author":"Hylands","year":"1985","journal-title":"Phytochemistry"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4188","DOI":"10.3390\/md12074188","article-title":"Pseudaboydins A and B: Novel Isobenzofuranone Derivatives from Marine Fungus Pseudallescheria Boydii Associated with Starfish Acanthaster Planci","volume":"12","author":"Lan","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0031-9422(88)80599-5","article-title":"A Highly Efficient Preparation of Lunularic Acid and Some Biological Activities of Stilbene and Dihydrostilbene Derivatives","volume":"27","author":"Hashimoto","year":"1988","journal-title":"Phytochemistry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"35481","DOI":"10.1039\/D3RA07503F","article-title":"Bio-Guided Isolation of Alpha-Glucosidase Inhibitory Compounds from Vietnamese Liverwort Marchantia polymorpha: In Vitro and In Silico Studies","volume":"13","author":"Nguyen","year":"2023","journal-title":"RSC Adv."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/0031-9422(71)85032-X","article-title":"Isolation and Structure of Two New Dihydroisocoumarins from Kigelia Pinnata","volume":"10","author":"Govindachari","year":"1971","journal-title":"Phytochemistry"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"107602","DOI":"10.1016\/j.isci.2023.107602","article-title":"Plant Flavonoid Inhibition of SARS-CoV-2 Main Protease and Viral Replication","volume":"26","author":"Lin","year":"2023","journal-title":"iScience"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s40199-023-00461-3","article-title":"Flavonoid as Possible Therapeutic Targets against COVID-19: A Scoping Review of In Silico Studies","volume":"31","author":"Toigo","year":"2023","journal-title":"DARU J. Pharm. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","article-title":"Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings","volume":"46","author":"Lipinski","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1517\/17460441.2012.714363","article-title":"The Influence of Lipophilicity in Drug Discovery and Development","volume":"7","author":"Arnott","year":"2012","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1021\/jm020017n","article-title":"Molecular Properties That Influence the Oral Bioavailability of Drug Candidates","volume":"45","author":"Veber","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1021\/cn100008c","article-title":"Moving beyond Rules: The Development of a Central Nervous System Multiparameter Optimization Approach to Enable Alignment of Druglike Properties","volume":"1","author":"Wager","year":"2010","journal-title":"ACS Chem. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"105","DOI":"10.56782\/pps.280","article-title":"Advances in Lopinavir Formulations: Strategies to Overcome Solubility, Bioavailability, and Stability Challenges","volume":"22","author":"Singireddy","year":"2024","journal-title":"Prospect. Pharm. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and Ligand Preparation: Parameters, Protocols, and Influence on Virtual Screening Enrichments","volume":"27","author":"Adzhigirey","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s12551-016-0247-1","article-title":"Software for Molecular Docking: A Review","volume":"9","author":"Pagadala","year":"2017","journal-title":"Biophys. Rev."},{"key":"ref_66","unstructured":"Schr\u00f6dinger, LLC (2025). Schr\u00f6dinger Release 2026-2: Glide, Schr\u00f6dinger, LLC."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/s42004-023-01019-9","article-title":"The Maximal and Current Accuracy of Rigorous Protein-Ligand Binding Free Energy Calculations","volume":"6","author":"Ross","year":"2023","journal-title":"Commun. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/12\/2009\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T16:26:01Z","timestamp":1780935961000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/12\/2009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,8]]},"references-count":67,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["molecules31122009"],"URL":"https:\/\/doi.org\/10.3390\/molecules31122009","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,8]]}}}