{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T14:39:48Z","timestamp":1783003188708,"version":"3.54.5"},"reference-count":119,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100010892","name":"Department of Science and Technology, Republic of the Philippines","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010892","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010217","name":"National Research Council of the Philippines","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010217","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-25354-0","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T12:28:30Z","timestamp":1763987310000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of SARS-CoV-2 3CLpro inhibitors from marine actinomycetes through integrated phylogeny-based metabolomics with functional screening and bioinformatic analysis"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2850-7797","authenticated-orcid":false,"given":"Doralyn S.","family":"Dalisay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jomari C.","family":"Mateo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jade Joshua R.","family":"Teodosio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucille Marie S.","family":"Jusa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane Monique S.","family":"Baladjay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leighiara S.","family":"de Guzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lex Aliko P.","family":"Balida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamia Azdina","family":"Jamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"25354_CR1","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1056\/NEJMoa2001017","volume":"382","author":"N Zhu","year":"2020","unstructured":"Zhu, N. et al. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 382, 727\u2013733 (2020).","journal-title":"N. Engl. J. Med."},{"key":"25354_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5582\/bst.2020.01056","volume":"14","author":"P Song","year":"2020","unstructured":"Song, P. & Karako, T. COVID-19: Real-time dissemination of scientific information to fight a public health emergency of international concern. Biosci. Trends 14, 1\u20132 (2020).","journal-title":"Biosci. Trends"},{"key":"25354_CR3","unstructured":"WHO. WHO COVID-19 Dashboard, accessed 14 September 2025; https:\/\/data.who.int\/dashboards\/covid19\/cases?n=o (2025)."},{"key":"25354_CR4","unstructured":"Davies, N. G. et al. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science 372, eabg3055 (2021)."},{"key":"25354_CR5","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1038\/s41586-021-03402-9","volume":"592","author":"H Tegally","year":"2021","unstructured":"Tegally, H. et al. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature 592, 438\u2013443 (2021).","journal-title":"Nature"},{"key":"25354_CR6","doi-asserted-by":"crossref","unstructured":"Hoffmann, M. et al. SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies. Cell 184, 2384\u20132393.e12 (2021).","DOI":"10.1016\/j.cell.2021.03.036"},{"key":"25354_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2022.119757","volume":"310","author":"M Joshi","year":"2022","unstructured":"Joshi, M. et al. Genetic sequencing detected the SARS-CoV-2 delta variant in wastewater a month prior to the first COVID-19 case in Ahmedabad (India). Environ. Pollut. 310, 119757 (2022).","journal-title":"Environ. Pollut."},{"key":"25354_CR8","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.3390\/v15051194","volume":"15","author":"K Subramoney","year":"2023","unstructured":"Subramoney, K. et al. Molecular epidemiology of SARS-CoV-2 during five COVID-19 waves and the significance of low-frequency lineages. Viruses 15, 1194 (2023).","journal-title":"Viruses"},{"key":"25354_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmni.2020.100673","volume":"35","author":"AA Dawood","year":"2020","unstructured":"Dawood, A. A. Mutated COVID. New Microbes New Infect. 35, 100673 (2020).","journal-title":"New Microbes New Infect."},{"key":"25354_CR10","doi-asserted-by":"publisher","first-page":"e00399","DOI":"10.1128\/AAC.00399-20","volume":"64","author":"MA Martinez","year":"2020","unstructured":"Martinez, M. A. Compounds with therapeutic potential against novel respiratory 2019 coronavirus. Antimicrob. Agents Chemother. 64, e00399-e420 (2020).","journal-title":"Antimicrob. Agents Chemother."},{"key":"25354_CR11","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1126\/science.abb3405","volume":"368","author":"L Zhang","year":"2020","unstructured":"Zhang, L. et al. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved \u03b1-ketoamide inhibitors. Science 368, 409\u2013412 (2020).","journal-title":"Science"},{"key":"25354_CR12","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.drudis.2015.01.009","volume":"21","author":"E Patridge","year":"2016","unstructured":"Patridge, E., Gareiss, P., Kinch, M. S. & Hoyer, D. An analysis of FDA-approved drugs: natural products and their derivatives. Drug Discov. Today 21, 204\u2013207 (2016).","journal-title":"Drug Discov. Today"},{"key":"25354_CR13","doi-asserted-by":"crossref","unstructured":"Farmer, P. B. & Suhadolnik, R. J. Nucleoside antibiotics. Biosynthesis of arabinofuranosyladenine by Streptomyces antibioticus. Biochemistry. 11, 911\u2013916 (1972).","DOI":"10.1021\/bi00755a034"},{"key":"25354_CR14","doi-asserted-by":"crossref","unstructured":"Farmer, P. B., Uematsu, T., Hogenkamp, H. P. & Suhadolnik, R. J. Nucleoside antibiotics. Epimerization of carbon 2\u2032 of adenosine during the biosynthesis of 9-\u03b2-D-arabinofuranosyladenine by Streptomyces antibioticus. J. Biol. Chem. 248, 1844\u20131847 (1973).","DOI":"10.1016\/S0021-9258(19)44267-1"},{"key":"25354_CR15","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/0923-2508(96)81068-0","volume":"146","author":"IS Novella","year":"1995","unstructured":"Novella, I. S. & S\u00e1nchez, J. Effects of 5-azacytidine on physiological differentiation of Streptomyces antibioticus. Res. Microbiol. 146, 721\u2013728 (1995).","journal-title":"Res. Microbiol."},{"key":"25354_CR16","doi-asserted-by":"crossref","unstructured":"Seley-Radtke, K. L. & Yates, M. K. The evolution of nucleoside analogue antivirals: A review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold. Antiviral Res. 154, 66\u201386 (2018).","DOI":"10.1016\/j.antiviral.2018.04.004"},{"key":"25354_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2020.104787","volume":"178","author":"L Caly","year":"2020","unstructured":"Caly, L., Druce, J. D., Catton, M. G., Jans, D. A. & Wagstaff, K. M. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 178, 104787 (2020).","journal-title":"Antiviral Res."},{"key":"25354_CR18","volume":"69","author":"R Cobos-Campos","year":"2021","unstructured":"Cobos-Campos, R. et al. Potential use of ivermectin for the treatment and prophylaxis of SARS-CoV-2 infection. Curr. Res. Transl. Med. 69, 103309 (2021).","journal-title":"Curr. Res. Transl. Med."},{"key":"25354_CR19","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1111\/fcp.12644","volume":"35","author":"RT Kinobe","year":"2021","unstructured":"Kinobe, R. T. & Owens, L. A systematic review of experimental evidence for antiviral effects of ivermectin and an in silico analysis of ivermectin\u2019s possible mode of action against SARS-CoV-2. Fundam. Clin. Pharmacol. 35, 260\u2013276 (2021).","journal-title":"Fundam. Clin. Pharmacol."},{"key":"25354_CR20","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1186\/s12879-022-07589-8","volume":"22","author":"MS Marcolino","year":"2022","unstructured":"Marcolino, M. S. et al. Systematic review and meta-analysis of ivermectin for treatment of COVID-19: evidence beyond the hype. BMC Infect. Dis. 22, 639 (2022).","journal-title":"BMC Infect. Dis."},{"key":"25354_CR21","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1186\/s12985-022-01829-8","volume":"19","author":"A Shafiee","year":"2022","unstructured":"Shafiee, A. et al. Ivermectin under scrutiny: a systematic review and meta-analysis of efficacy and possible sources of controversies in COVID-19 patients. Virol. J. 19, 102 (2022).","journal-title":"Virol. J."},{"key":"25354_CR22","doi-asserted-by":"crossref","unstructured":"Tenebro, C. P. et al. Synergy between genome mining, metabolomics, and bioinformatics uncovers antibacterial chlorinated carbazole alkaloids and their biosynthetic gene cluster from Streptomyces tubbatahanensis sp. nov., a novel actinomycete isolated from Sulu Sea, Philippines. Microbiol. Spectr. 0, e03661\u201322 (2023).","DOI":"10.1128\/spectrum.03661-22"},{"key":"25354_CR23","first-page":"98601","volume":"11","author":"CP Tenebro","year":"2021","unstructured":"Tenebro, C. P. et al. Multiple strain analysis of Streptomyces species from Philippine marine sediments reveals intraspecies heterogeneity in antibiotic activities. Sci. Rep. 11, 98601 (2021).","journal-title":"Sci. Rep."},{"key":"25354_CR24","doi-asserted-by":"publisher","first-page":"441","DOI":"10.3390\/md19080441","volume":"19","author":"EM Sabido","year":"2021","unstructured":"Sabido, E. M. et al. Insights into the variation in bioactivities of closely related Streptomyces strains from marine sediments of the Visayan Sea against ESKAPE and ovarian cancer. Mar. Drugs. 19, 441 (2021).","journal-title":"Mar. Drugs."},{"key":"25354_CR25","doi-asserted-by":"publisher","first-page":"734","DOI":"10.3390\/jmse8100734","volume":"8","author":"EM Sabido","year":"2020","unstructured":"Sabido, E. M. et al. Marine sediment-derived Streptomyces strain produces angucycline antibiotics against multidrug-resistant Staphylococcus aureus harboring SCCmec type 1 gene. J. Mar. Sci. Eng. 8, 734 (2020).","journal-title":"J. Mar. Sci. Eng."},{"key":"25354_CR26","doi-asserted-by":"publisher","first-page":"743","DOI":"10.3389\/fmicb.2020.00743","volume":"11","author":"MJV Paderog","year":"2020","unstructured":"Paderog, M. J. V. et al. Anthracycline shunt metabolites from Philippine marine sediment-derived Streptomyces destroy cell membrane integrity of multidrug-resistant Staphylococcus aureus. Front. Microbiol. 11, 743 (2020).","journal-title":"Front. Microbiol."},{"key":"25354_CR27","doi-asserted-by":"publisher","first-page":"872","DOI":"10.3389\/fmicb.2015.00872","volume":"6","author":"SA Carr","year":"2015","unstructured":"Carr, S. A., Orcutt, B. N., Mandernack, K. W. & Spear, J. R. Abundant Atribacteria in deep marine sediment from the Ad\u00e9lie Basin, Antarctica. Front. Microbiol. 6, 872 (2015).","journal-title":"Front. Microbiol."},{"key":"25354_CR28","doi-asserted-by":"publisher","first-page":"758","DOI":"10.3389\/fmicb.2019.00758","volume":"10","author":"C Petro","year":"2019","unstructured":"Petro, C. et al. Marine deep biosphere microbial communities assemble in near-surface sediments in Aarhus Bay. Front. Microbiol. 10, 758 (2019).","journal-title":"Front. Microbiol."},{"key":"25354_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2024.168474","volume":"436","author":"C Lin","year":"2024","unstructured":"Lin, C. et al. Structural basis for coronaviral main proteases inhibition by the 3CLpro inhibitor GC376. J. Mol. Biol. 436, 168474 (2024).","journal-title":"J. Mol. Biol."},{"key":"25354_CR30","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2022.852210","volume":"10","author":"J Lu","year":"2022","unstructured":"Lu, J. et al. Crystallization of feline coronavirus M. Front. Chem. 10, 852210 (2022).","journal-title":"Front. Chem."},{"key":"25354_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2021.105183","volume":"195","author":"R Dey-Rao","year":"2021","unstructured":"Dey-Rao, R. et al. A fluorescence-based, gain-of-signal, live cell system to evaluate SARS-CoV-2 main protease inhibition. Antiviral Res. 195, 105183 (2021).","journal-title":"Antiviral Res."},{"key":"25354_CR32","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1021\/acsptsci.0c00108","volume":"3","author":"W Zhu","year":"2020","unstructured":"Zhu, W. et al. Identification of SARS-CoV-2 3CL protease inhibitors by a quantitative high-throughput screening. ACS Pharmacol. Transl. Sci. 3, 1008\u20131016 (2020).","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"25354_CR33","doi-asserted-by":"publisher","first-page":"3022","DOI":"10.1093\/molbev\/msab120","volume":"38","author":"K Tamura","year":"2021","unstructured":"Tamura, K., Stecher, G. & Kumar, S. MEGA11: molecular evolutionary genetics analysis version 11. Mol. Biol. Evol. 38, 3022\u20133027 (2021).","journal-title":"Mol. Biol. Evol."},{"key":"25354_CR34","first-page":"406","volume":"4","author":"N Saitou","year":"1987","unstructured":"Saitou, N. & Nei, M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol. 4, 406\u2013425 (1987).","journal-title":"Mol. Biol. Evol."},{"key":"25354_CR35","first-page":"512","volume":"10","author":"K Tamura","year":"1993","unstructured":"Tamura, K. & Nei, M. Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. Mol. Biol. Evol. 10, 512\u2013526 (1993).","journal-title":"Mol. Biol. Evol."},{"key":"25354_CR36","doi-asserted-by":"publisher","first-page":"W78","DOI":"10.1093\/nar\/gkae268","volume":"52","author":"I Letunic","year":"2024","unstructured":"Letunic, I. & Bork, P. Interactive Tree of Life (iTOL) v6: Recent updates to the phylogenetic tree display and annotation tool. Nucleic Acids Res. 52, W78\u2013W82 (2024).","journal-title":"Nucleic Acids Res."},{"key":"25354_CR37","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1021\/ed100697w","volume":"87","author":"HE Pence","year":"2010","unstructured":"Pence, H. E. & Williams, A. ChemSpider: An online chemical information resource. J. Chem. Educ. 87, 1123\u20131124 (2010).","journal-title":"J. Chem. Educ."},{"key":"25354_CR38","doi-asserted-by":"publisher","first-page":"D1388","DOI":"10.1093\/nar\/gkaa971","volume":"49","author":"S Kim","year":"2021","unstructured":"Kim, S. et al. PubChem in 2021: New data content and improved web interfaces. Nucleic Acids Res. 49, D1388\u2013D1395 (2021).","journal-title":"Nucleic Acids Res."},{"key":"25354_CR39","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1038\/nbt.3597","volume":"34","author":"M Wang","year":"2016","unstructured":"Wang, M. et al. Sharing and community curation of mass spectrometry data with global natural products social molecular networking. Nat. Biotechnol. 34, 828\u2013837 (2016).","journal-title":"Nat. Biotechnol."},{"key":"25354_CR40","doi-asserted-by":"publisher","unstructured":"Poynton, E. F. et al. The Natural Products Atlas 3.0: extending the database of microbially derived natural products. Nucleic Acids Res. https:\/\/doi.org\/10.1093\/nar\/gkae1093 (2024).","DOI":"10.1093\/nar\/gkae1093"},{"key":"25354_CR41","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1186\/s12859-019-2954-7","volume":"20","author":"C Ruttkies","year":"2019","unstructured":"Ruttkies, C., Neumann, S. & Posch, S. Improving MetFrag with statistical learning of fragment annotations. BMC Bioinform. 20, 376 (2019).","journal-title":"BMC Bioinform."},{"key":"25354_CR42","doi-asserted-by":"publisher","unstructured":"Feng, Y. et al. StreptomeDB 4.0: A comprehensive database of streptomycetes natural products enriched with protein interactions and interactive spectral visualization. Nucleic Acids Res. https:\/\/doi.org\/10.1093\/nar\/gkae1030 (2024).","DOI":"10.1093\/nar\/gkae1030"},{"key":"25354_CR43","doi-asserted-by":"publisher","unstructured":"Jim\u00e9nez-Avalos, G., Vargas-Ruiz, A. P., Delgado-Pease, N. E., Olivos-Ramirez, G. E., Sheen, P., Fern\u00e1ndez-D\u00edaz, M., Quiliano, M., Zimic, M. & Per\u00fa, C.-W. G. I. Comprehensive virtual screening of 4.8 k flavonoids reveals novel insights into allosteric inhibition of SARS-CoV-2 MPro Sci. Rep. 11, 15452 (2021). https:\/\/doi.org\/10.1038\/s41598-021-94951-6","DOI":"10.1038\/s41598-021-94951-6"},{"key":"25354_CR44","doi-asserted-by":"publisher","unstructured":"Banerjee, P., Kemmler, E., Dunkel, M. & Preissner, R. ProTox 3.0: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. https:\/\/doi.org\/10.1093\/nar\/gkae303 (2024).","DOI":"10.1093\/nar\/gkae303"},{"key":"25354_CR45","doi-asserted-by":"crossref","unstructured":"Williams, D. E. et al. Aminorifamycins and sporalactams produced in culture by a Micromonospora sp. isolated from a northeastern-Pacific marine sediment are potent antibiotics. Org. Lett. 19, 766\u2013769 (2017).","DOI":"10.1021\/acs.orglett.6b03619"},{"key":"25354_CR46","doi-asserted-by":"crossref","unstructured":"Williams, D. E. et al. Structures of Nahuoic Acids B\u2013E produced in culture by a Streptomyces sp. isolated from a marine sediment and evidence for the inhibition of the histone methyl transferase SETD8 in human cancer cells by Nahuoic Acid A. J. Org. Chem. 81, 1324\u20131332 (2016).","DOI":"10.1021\/acs.joc.5b02569"},{"key":"25354_CR47","doi-asserted-by":"crossref","unstructured":"Williams, D. E. et al. Padanamides A and B, highly modified linear tetrapeptides produced in culture by a Streptomyces sp. isolated from a marine sediment. Org. Lett. 13, 3936\u20133939 (2011).","DOI":"10.1021\/ol2014494"},{"key":"25354_CR48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/MMBR.00019-15","volume":"80","author":"EA Barka","year":"2016","unstructured":"Barka, E. A. et al. Taxonomy, physiology, and natural products of actinobacteria. Microbiol. Mol. Biol. Rev. 80, 1\u201343 (2016).","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"25354_CR49","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1128\/MMBR.00005-07","volume":"71","author":"M Ventura","year":"2007","unstructured":"Ventura, M. et al. Genomics of actinobacteria: tracing the evolutionary history of an ancient phylum. Microbiol. Mol. Biol. Rev. 71, 495\u2013548 (2007).","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"25354_CR50","doi-asserted-by":"publisher","first-page":"e00872","DOI":"10.1128\/AAC.00872-20","volume":"64","author":"H-C Hung","year":"2020","unstructured":"Hung, H.-C. et al. Discovery of M protease inhibitors encoded by SARS-CoV-2. Antimicrob. Agents Chemother. 64, e00872-e920 (2020).","journal-title":"Antimicrob. Agents Chemother."},{"key":"25354_CR51","doi-asserted-by":"publisher","first-page":"4417","DOI":"10.1038\/s41467-020-18233-x","volume":"11","author":"L Fu","year":"2020","unstructured":"Fu, L. et al. Both boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease. Nat. Commun. 11, 4417 (2020).","journal-title":"Nat. Commun."},{"key":"25354_CR52","unstructured":"Nolasco, B., Villal\u00f3n, A., National Commission on Culture and the Arts (Philippines) & LC Exchange Collection (Library of Congress). Legacy: Philippine world heritage sites. (National Commission for Culture and the Arts, Manila, 2003)."},{"key":"25354_CR53","unstructured":"Arquiza, Y. & White, A. T. Tales from Tubbataha: Natural History, Resource Use, and Conservation of the Tubbataha Reefs, Palawan, Philippines. (Bandillo ng Palawan Foundation, 1994)."},{"key":"25354_CR54","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1016\/j.marpolbul.2016.10.017","volume":"114","author":"WY Licuanan","year":"2017","unstructured":"Licuanan, W. Y., Robles, R., Dygico, M., Songco, A. & van Woesik, R. Coral benchmarks in the center of biodiversity. Mar. Pollut. Bull. 114, 1135\u20131140 (2017).","journal-title":"Mar. Pollut. Bull."},{"key":"25354_CR55","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/1471-2148-12-171","volume":"12","author":"RP Lamers","year":"2012","unstructured":"Lamers, R. P. et al. Phylogenetic relationships among Staphylococcus species and refinement of cluster groups based on multilocus data. BMC Evol. Biol. 12, 171 (2012).","journal-title":"BMC Evol. Biol."},{"key":"25354_CR56","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1101\/gr.187002","volume":"12","author":"V Daubin","year":"2002","unstructured":"Daubin, V., Gouy, M. & Perri\u00e8re, G. A phylogenomic approach to bacterial phylogeny: evidence of a core of genes sharing a common history. Genome Res. 12, 1080\u20131090 (2002).","journal-title":"Genome Res."},{"key":"25354_CR57","doi-asserted-by":"publisher","first-page":"281","DOI":"10.3389\/fmicb.2015.00281","volume":"6","author":"S Spring","year":"2015","unstructured":"Spring, S., Scheuner, C., G\u00f6ker, M. & Klenk, H. P. A taxonomic framework for emerging groups of ecologically important marine gammaproteobacteria based on the reconstruction of evolutionary relationships using genome-scale data. Front. Microbiol. 6, 281 (2015).","journal-title":"Front. Microbiol."},{"key":"25354_CR58","doi-asserted-by":"crossref","unstructured":"Kumar, P., Kundu, A., Kumar, M., Solanki, R. & Kapur, M. K. Exploitation of potential bioactive compounds from two soil-derived actinomycetes, Streptomyces sp. strain 196 and RI.24. Microbiol. Res. 229, 126312 (2019).","DOI":"10.1016\/j.micres.2019.126312"},{"key":"25354_CR59","doi-asserted-by":"publisher","first-page":"13779","DOI":"10.3390\/ijms232213779","volume":"23","author":"CV Anh","year":"2022","unstructured":"Anh, C. V. et al. New angucycline glycosides from a marine-derived bacterium. Int. J. Mol. Sci. 23, 13779 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"25354_CR60","doi-asserted-by":"crossref","unstructured":"Li, Y. et al. Diastaphenazine, a new dimeric phenazine from an endophytic Streptomyces diastaticus subsp. ardesiacus. J. Antibiot. (Tokyo) 68, 210\u2013212 (2015).","DOI":"10.1038\/ja.2014.124"},{"key":"25354_CR61","doi-asserted-by":"crossref","unstructured":"Moumbock, A. F. A. et al. StreptomeDB 3.0: an updated compendium of streptomycetes natural products. Nucleic Acids Res. 49, D600-D604 (2021).","DOI":"10.1093\/nar\/gkaa868"},{"key":"25354_CR62","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.fsi.2019.10.055","volume":"95","author":"M Libr\u00e1n-P\u00e9rez","year":"2019","unstructured":"Libr\u00e1n-P\u00e9rez, M., Pereiro, P., Figueras, A. & Novoa, B. Antiviral activity of palmitic acid via autophagic flux inhibition in zebrafish (Danio rerio). Fish Shellfish Immunol. 95, 595\u2013605 (2019).","journal-title":"Fish Shellfish Immunol."},{"key":"25354_CR63","doi-asserted-by":"crossref","unstructured":"Yang, Z., Shao, L., Wang, M., Rao, M., Ge, M. & Xu, Y. Two novel quinomycins discovered by UPLC-MS from Streptomyces sp. HCCB11876. J. Antibiot. (Tokyo) 72, 164\u2013168 (2019).","DOI":"10.1038\/s41429-018-0132-1"},{"key":"25354_CR64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.trac.2011.08.009","volume":"32","author":"JF Xiao","year":"2012","unstructured":"Xiao, J. F., Zhou, B. & Ressom, H. W. Metabolite identification and quantitation in LC-MS\/MS-based metabolomics. TrAC Trends Analyt. Chem. 32, 1\u201314 (2012).","journal-title":"TrAC Trends Analyt. Chem."},{"key":"25354_CR65","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s11306-022-01874-y","volume":"18","author":"LM Bayona","year":"2022","unstructured":"Bayona, L. M., de Voogd, N. J. & Choi, Y. H. Metabolomics on the study of marine organisms. Metabolomics 18, 17 (2022).","journal-title":"Metabolomics"},{"key":"25354_CR66","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1039\/C9NP00048H","volume":"37","author":"MG Chevrette","year":"2020","unstructured":"Chevrette, M. G. et al. Evolutionary dynamics of natural product biosynthesis in bacteria. Nat. Prod. Rep. 37, 566\u2013599 (2020).","journal-title":"Nat. Prod. Rep."},{"key":"25354_CR67","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1093\/molbev\/msi193","volume":"22","author":"H Jenke-Kodama","year":"2005","unstructured":"Jenke-Kodama, H., Sandmann, A., M\u00fcller, R. & Dittmann, E. Evolutionary implications of bacterial polyketide synthases. Mol. Biol. Evol. 22, 2027\u20132039 (2005).","journal-title":"Mol. Biol. Evol."},{"key":"25354_CR68","volume":"5","author":"N S\u00e9lem-Mojica","year":"2019","unstructured":"S\u00e9lem-Mojica, N. et al. EvoMining reveals the origin and fate of natural product biosynthetic enzymes. Microb. Genom. 5, e000260 (2019).","journal-title":"Microb. Genom."},{"key":"25354_CR69","doi-asserted-by":"publisher","first-page":"2062","DOI":"10.3390\/microorganisms9102062","volume":"9","author":"I Kolouchov\u00e1","year":"2021","unstructured":"Kolouchov\u00e1, I., Timkina, E., Ma\u0165\u00e1tkov\u00e1, O., Kyselov\u00e1, L. & \u0158ezanka, T. Analysis of bacteriohopanoids from thermophilic bacteria by liquid chromatography-mass spectrometry. Microorganisms. 9, 2062 (2021).","journal-title":"Microorganisms."},{"key":"25354_CR70","doi-asserted-by":"crossref","unstructured":"Rohmer, M., Sutter, B. & Sahm, H. Bacterial sterol surrogates. Biosynthesis of the side-chain of bacteriohopanetetrol and of a carbocyclic pseudopentose from 13C-labelled glucose in Zymomonas mobilis. J. Chem. Soc., Chem. Commun. 1989, 1471\u20131472 (1989).","DOI":"10.1039\/c39890001471"},{"key":"25354_CR71","doi-asserted-by":"crossref","unstructured":"Ourisson, G. & Rohmer, M. Hopanoids. 2. Biohopanoids: A novel class of bacterial lipids. Acc. Chem. Res. 25, 403\u2013408 (1992).","DOI":"10.1021\/ar00021a004"},{"key":"25354_CR72","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1111\/j.1574-6968.2000.tb09212.x","volume":"189","author":"K Poralla","year":"2000","unstructured":"Poralla, K., Muth, G. & H\u00e4rtner, T. Hopanoids are formed during transition from substrate to aerial hyphae in Streptomyces coelicolor A3(2). FEMS Microbiol. Lett. 189, 93\u201395 (2000).","journal-title":"FEMS Microbiol. Lett."},{"key":"25354_CR73","doi-asserted-by":"publisher","first-page":"705","DOI":"10.3390\/md8030705","volume":"8","author":"CC de Carvalho","year":"2010","unstructured":"de Carvalho, C. C. & Fernandes, P. Production of metabolites as bacterial responses to the marine environment. Mar. Drugs. 8, 705\u2013727 (2010).","journal-title":"Mar. Drugs."},{"key":"25354_CR74","doi-asserted-by":"crossref","unstructured":"Ourisson, G. & Albrecht, P. Hopanoids. 1. Geohopanoids: The most abundant natural products on Earth? Acc. Chem. Res. 25, 398\u2013402 (1992).","DOI":"10.1021\/ar00021a003"},{"key":"25354_CR75","unstructured":"Kim, H.-J., Hwang, S.-E., Heo, J.T., Kim, C.-J. & Ryu, J.-R. Production of oleamide, a functional lipid, by Streptomyces sp. KK90378. J. Microbiol. Biotechnol. 11, 1018\u20131023 (2001)."},{"key":"25354_CR76","doi-asserted-by":"crossref","unstructured":"Tanvir, R., Sajid, I., Rehman, Y. & Hasnain, S. Fatty acid based antimicrobials from Streptomyces sp. SORS-24, an endophyte isolated from Sonchus oleraceus. Lett. Appl. Microbiol. 76, (2023).","DOI":"10.1093\/lambio\/ovad080"},{"key":"25354_CR77","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1111\/j.1574-6976.2010.00259.x","volume":"35","author":"G Gago","year":"2011","unstructured":"Gago, G., Diacovich, L., Arabolaza, A., Tsai, S.-C. & Gramajo, H. Fatty acid biosynthesis in actinomycetes. FEMS Microbiol. Rev. 35, 475\u2013497 (2011).","journal-title":"FEMS Microbiol. Rev."},{"key":"25354_CR78","doi-asserted-by":"crossref","unstructured":"Schneider, O. et al. Genomics-based insights into the biosynthesis and unusually high accumulation of free fatty acids by Streptomyces sp. NP10. Front. Microbiol. 9, 1302 (2018).","DOI":"10.3389\/fmicb.2018.01302"},{"key":"25354_CR79","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1186\/s12934-024-02527-6","volume":"23","author":"X Xu","year":"2024","unstructured":"Xu, X. et al. Regulatory mechanism of C4-dicarboxylates in cyclo(Phe-Pro) production. Microb. Cell Fact. 23, 255 (2024).","journal-title":"Microb. Cell Fact."},{"key":"25354_CR80","doi-asserted-by":"crossref","unstructured":"Nadal Jimenez, P. et al. The multiple signaling systems regulating virulence in Pseudomonas aeruginosa. Microbiol. Mol. Biol. Rev. 76, 46\u201365 (2012).","DOI":"10.1128\/MMBR.05007-11"},{"key":"25354_CR81","doi-asserted-by":"publisher","first-page":"2214","DOI":"10.1128\/JB.188.6.2214-2221.2006","volume":"188","author":"DK Park","year":"2006","unstructured":"Park, D. K. et al. Cyclo(Phe-Pro) modulates the expression of ompU in Vibrio spp.. J. Bacteriol. 188, 2214\u20132221 (2006).","journal-title":"J. Bacteriol."},{"key":"25354_CR82","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1046\/j.1365-2958.1999.01577.x","volume":"33","author":"MTG Holden","year":"1999","unstructured":"Holden, M. T. G. et al. Quorum-sensing cross talk: isolation and chemical characterization of cyclic dipeptides from Pseudomonas aeruginosa and other gram-negative bacteria. Mol. Microbiol. 33, 1254\u20131266 (1999).","journal-title":"Mol. Microbiol."},{"key":"25354_CR83","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1007\/s10126-014-9559-y","volume":"16","author":"C Brack","year":"2014","unstructured":"Brack, C., Mikolasch, A. & Schauer, F. 2,5-Diketopiperazines produced by Bacillus pumilus during bacteriolysis of Arthrobacter citreus. Mar. Biotechnol. 16, 385\u2013395 (2014).","journal-title":"Mar. Biotechnol."},{"key":"25354_CR84","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/ja.2014.86","volume":"68","author":"B Matselyukh","year":"2015","unstructured":"Matselyukh, B. et al. N-methylphenylalanyl-dehydrobutyrine diketopiperazine, an A-factor mimic that restores antibiotic biosynthesis and morphogenesis in Streptomyces globisporus 1912\u2013B2 and Streptomyces griseus 1439. J. Antibiot. 68, 9\u201314 (2015).","journal-title":"J. Antibiot."},{"key":"25354_CR85","doi-asserted-by":"crossref","unstructured":"Chen, L. et al. Cytotoxic bagremycins from mangrove-derived Streptomyces sp. Q22. J. Nat. Prod. 80, 1450\u20131456 (2017).","DOI":"10.1021\/acs.jnatprod.6b01136"},{"key":"25354_CR86","doi-asserted-by":"crossref","unstructured":"Driche, E. H. et al. A new Saharan strain of Streptomyces sp. GSB-11 produces maculosin and N-acetyltyramine active against multidrug-resistant pathogenic bacteria. Curr. Microbiol. 79, 298 (2022).","DOI":"10.1007\/s00284-022-02994-3"},{"key":"25354_CR87","doi-asserted-by":"crossref","unstructured":"Liu, N. et al. Streptomyces alni sp. nov., a daidzein-producing endophyte isolated from a root of Alnus nepalensis D. Don. Int. J. Syst. Evol. Microbiol. 59, 254\u2013258 (2009).","DOI":"10.1099\/ijs.0.65769-0"},{"key":"25354_CR88","doi-asserted-by":"publisher","first-page":"973","DOI":"10.7164\/antibiotics.53.973","volume":"53","author":"B Schlegel","year":"2000","unstructured":"Schlegel, B., Luhmann, U., H\u00e4rtl, A. & Gr\u00e4fe, U. Piptamine, a new antibiotic produced by Piptoporus betulinus Lu 9\u20131. J. Antibiot. 53, 973\u2013974 (2000).","journal-title":"J. Antibiot."},{"key":"25354_CR89","doi-asserted-by":"publisher","first-page":"2501","DOI":"10.1021\/acs.jnatprod.0c00486","volume":"83","author":"T Cheng","year":"2020","unstructured":"Cheng, T. et al. Heimiomycins A-C and calamenens from the African basidiomycete Heimiomyces sp. J. Nat. Prod. 83, 2501\u20132507 (2020).","journal-title":"J. Nat. Prod."},{"key":"25354_CR90","doi-asserted-by":"crossref","unstructured":"Song, Y. et al. Cytotoxic and antibacterial angucycline- and prodigiosin-analogues from the deep-sea derived Streptomyces sp. SCSIO 11594. Mar. Drugs. 13, 1304\u20131316 (2015).","DOI":"10.3390\/md13031304"},{"key":"25354_CR91","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1021\/acs.orglett.5b03609","volume":"18","author":"Z Zhao","year":"2016","unstructured":"Zhao, Z. et al. Hybrubins: bipyrrole tetramic acids obtained by crosstalk between a truncated undecylprodigiosin pathway and heterologous tetramic acid biosynthetic genes. Org. Lett. 18, 572\u2013575 (2016).","journal-title":"Org. Lett."},{"key":"25354_CR92","doi-asserted-by":"publisher","first-page":"25978","DOI":"10.1074\/jbc.M110.142604","volume":"285","author":"TA Dailey","year":"2010","unstructured":"Dailey, T. A. et al. Discovery and characterization of HemQ: an essential heme biosynthetic pathway component. J. Biol. Chem. 285, 25978\u201325986 (2010).","journal-title":"J. Biol. Chem."},{"key":"25354_CR93","doi-asserted-by":"publisher","first-page":"2210","DOI":"10.1073\/pnas.1416285112","volume":"112","author":"HA Dailey","year":"2015","unstructured":"Dailey, H. A. et al. Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin. Proc. Natl Acad. Sci. USA 112, 2210\u20132215 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"25354_CR94","doi-asserted-by":"publisher","first-page":"e00048","DOI":"10.1128\/MMBR.00048-16","volume":"81","author":"HA Dailey","year":"2017","unstructured":"Dailey, H. A. et al. Prokaryotic heme biosynthesis: multiple pathways to a common essential product. Microbiol. Mol. Biol. Rev. 81, e00048-e116 (2017).","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"25354_CR95","doi-asserted-by":"publisher","first-page":"8183","DOI":"10.1074\/jbc.M710421200","volume":"283","author":"B Zhao","year":"2008","unstructured":"Zhao, B. et al. Biosynthesis of the sesquiterpene antibiotic albaflavenone in Streptomyces coelicolor A3(2). J. Biol. Chem. 283, 8183\u20138189 (2008).","journal-title":"J. Biol. Chem."},{"key":"25354_CR96","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1007\/s00253-019-10240-3","volume":"104","author":"SM Guzm\u00e1n-Trampe","year":"2020","unstructured":"Guzm\u00e1n-Trampe, S. M. et al. Production of distinct labdane-type diterpenoids using a novel cryptic labdane-like cluster from Streptomyces thermocarboxydus K155. Appl. Microbiol. Biotechnol. 104, 741\u2013750 (2020).","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"25354_CR97","doi-asserted-by":"publisher","first-page":"434","DOI":"10.7164\/antibiotics.47.434","volume":"47","author":"H G\u00fcrtler","year":"1994","unstructured":"G\u00fcrtler, H. et al. Albaflavenone, a sesquiterpene ketone with a zizaene skeleton produced by a streptomycete with a new rope morphology. J. Antibiot. 47, 434\u2013439 (1994).","journal-title":"J. Antibiot."},{"key":"25354_CR98","doi-asserted-by":"crossref","unstructured":"Jeong, S. Y. et al. Streptokordin, a new cytotoxic compound of the methylpyridine class from a marine-derived Streptomyces sp. KORDI-3238. J. Antibiot. 59, 234\u2013240 (2006).","DOI":"10.1038\/ja.2006.33"},{"key":"25354_CR99","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s12539-013-0146-0","volume":"5","author":"AR Lankapalli","year":"2013","unstructured":"Lankapalli, A. R. & Kannabiran, K. Interaction of marine Streptomyces compounds with selected cancer drug target proteins by in silico molecular docking studies. Interdiscip. Sci. 5, 37\u201344 (2013).","journal-title":"Interdiscip. Sci."},{"key":"25354_CR100","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.1021\/acs.jnatprod.0c00279","volume":"83","author":"DL Kukla","year":"2020","unstructured":"Kukla, D. L., Canchola, J. & Mills, J. J. Synthesis of the cyanobacterial antibiotics anaephenes A and B. J. Nat. Prod. 83, 2036\u20132040 (2020).","journal-title":"J. Nat. Prod."},{"key":"25354_CR101","doi-asserted-by":"crossref","unstructured":"Brumley, D. et al. Isolation and characterization of anaephenes A-C, alkylphenols from a filamentous cyanobacterium (Hormoscilla sp., Oscillatoriales). J. Nat. Prod. 81, 2716\u20132721 (2018).","DOI":"10.1021\/acs.jnatprod.8b00650"},{"key":"25354_CR102","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.3389\/fmicb.2018.01767","volume":"9","author":"R Singh","year":"2018","unstructured":"Singh, R. & Dubey, A. K. Diversity and applications of endophytic actinobacteria of plants in special and other ecological niches. Front. Microbiol. 9, 1767 (2018).","journal-title":"Front. Microbiol."},{"key":"25354_CR103","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.micres.2016.01.003","volume":"185","author":"R Tanvir","year":"2016","unstructured":"Tanvir, R., Sajid, I., Hasnain, S., Kulik, A. & Grond, S. Rare actinomycetes Nocardia caishijiensis and Pseudonocardia carboxydivorans as endophytes, their bioactivity and metabolites evaluation. Microbiol. Res. 185, 22\u201335 (2016).","journal-title":"Microbiol. Res."},{"key":"25354_CR104","doi-asserted-by":"publisher","first-page":"2422","DOI":"10.1021\/ol3008638","volume":"14","author":"P Fu","year":"2012","unstructured":"Fu, P. et al. Streptocarbazoles A and B, two novel indolocarbazoles from the marine-derived actinomycete strain Streptomyces sp. FMA. Org. Lett. 14, 2422\u20132425 (2012).","journal-title":"FMA. Org. Lett."},{"key":"25354_CR105","doi-asserted-by":"publisher","first-page":"3193","DOI":"10.1021\/cr200447s","volume":"112","author":"AW Schmidt","year":"2012","unstructured":"Schmidt, A. W., Reddy, K. R. & Kn\u00f6lker, H. J. Occurrence, biogenesis, and synthesis of biologically active carbazole alkaloids. Chem. Rev. 112, 3193\u20133328 (2012).","journal-title":"Chem. Rev."},{"key":"25354_CR106","doi-asserted-by":"publisher","DOI":"10.1128\/aem.02187-23","volume":"90","author":"F Xiao","year":"2024","unstructured":"Xiao, F. et al. Generation of streptocarbazoles with cytotoxicities by pathway engineering and insights into their biosynthesis. Appl. Environ. Microbiol. 90, e0218723 (2024).","journal-title":"Appl. Environ. Microbiol."},{"key":"25354_CR107","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1128\/jcm.33.5.1243-1246.1995","volume":"33","author":"C S\u00e1nchez","year":"1995","unstructured":"S\u00e1nchez, C. et al. The biosynthetic gene cluster for the antitumor rebeccamycin: characterization and generation of indolocarbazole derivatives. J. Clin. Microbiol. 33, 1243\u20131246 (1995).","journal-title":"J. Clin. Microbiol."},{"key":"25354_CR108","doi-asserted-by":"publisher","first-page":"2969","DOI":"10.1099\/mic.0.29043-0","volume":"152","author":"X Yin","year":"2006","unstructured":"Yin, X. & Zabriskie, T. M. The enduracidin biosynthetic gene cluster from Streptomyces fungicidicus. Microbiology 152, 2969\u20132983 (2006).","journal-title":"Microbiology"},{"key":"25354_CR109","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1016\/S1074-5521(02)00252-1","volume":"9","author":"Z Hojati","year":"2002","unstructured":"Hojati, Z. et al. Structure, biosynthetic origin, and engineered biosynthesis of calcium-dependent antibiotics from Streptomyces coelicolor. Chem. Biol. 9, 1175\u20131187 (2002).","journal-title":"Chem. Biol."},{"key":"25354_CR110","doi-asserted-by":"publisher","first-page":"14683","DOI":"10.1038\/s41598-022-14395-4","volume":"12","author":"E Elhaik","year":"2022","unstructured":"Elhaik, E. Principal component analyses (PCA)-based findings in population genetic studies are highly biased and must be reevaluated. Sci. Rep. 12, 14683 (2022).","journal-title":"Sci. Rep."},{"key":"25354_CR111","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1093\/sysbio\/syv019","volume":"64","author":"JC Uyeda","year":"2015","unstructured":"Uyeda, J. C., Caetano, D. S. & Pennell, M. W. Comparative analysis of principal components can be misleading. Syst. Biol. 64, 677\u2013689 (2015).","journal-title":"Syst. Biol."},{"key":"25354_CR112","first-page":"341","volume":"21","author":"M Bylesj\u00f6","year":"2007","unstructured":"Bylesj\u00f6, M. et al. OPLS discriminant analysis: Combining the strengths of PLS-DA and SIMCA classification. J. Chemom. 21, 341\u2013351 (2007).","journal-title":"J. Chemom."},{"key":"25354_CR113","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemolab.2025.105381","volume":"261","author":"I Ramtanon","year":"2025","unstructured":"Ramtanon, I., Lacoue-N\u00e8gre, M., Berlioz-Barbier, A., Le Masle, A. & Renault, J.-H. A selective genetic algorithm\u2013PLS-DA approach based on untargeted LC-HRMS: Application to complex biomass samples. Chemom. Intell. Lab. Syst. 261, 105381 (2025).","journal-title":"Chemom. Intell. Lab. Syst."},{"key":"25354_CR114","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.3390\/app13031522","volume":"13","author":"MG Bonomo","year":"2023","unstructured":"Bonomo, M. G. et al. An update of carbazole treatment strategies for COVID-19 infection. Appl. Sci. 13, 2023 (2023).","journal-title":"Appl. Sci."},{"key":"25354_CR115","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.3390\/molecules24101912","volume":"24","author":"A Caruso","year":"2019","unstructured":"Caruso, A. et al. Carbazole derivatives as antiviral agents: An overview. Molecules 24, 1012 (2019).","journal-title":"Molecules"},{"key":"25354_CR116","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1039\/D0MD00288G","volume":"11","author":"A Dorababu","year":"2020","unstructured":"Dorababu, A. Indole\u2014A promising pharmacophore in recent antiviral drug discovery. RSC Med. Chem. 11, 1335\u20131353 (2020).","journal-title":"RSC Med. Chem."},{"key":"25354_CR117","doi-asserted-by":"publisher","first-page":"746","DOI":"10.3390\/biom12060746","volume":"12","author":"B Tang","year":"2022","unstructured":"Tang, B. et al. AI-aided design of novel targeted covalent inhibitors against SARS-CoV-2. Biomolecules 12, 746 (2022).","journal-title":"Biomolecules"},{"key":"25354_CR118","doi-asserted-by":"publisher","first-page":"942","DOI":"10.3390\/v12090942","volume":"12","author":"SV Stoddard","year":"2020","unstructured":"Stoddard, S. V. et al. Optimization rules for SARS-CoV-2 M(pro) antivirals: ensemble docking and exploration of the coronavirus protease active site. Viruses 12, 942 (2020).","journal-title":"Viruses"},{"key":"25354_CR119","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.2147\/DDDT.S359009","volume":"16","author":"J Zhu","year":"2022","unstructured":"Zhu, J. et al. Progress on SARS-CoV-2 3CLpro inhibitors: inspiration from SARS-CoV 3CLpro peptidomimetics and small-molecule anti-inflammatory compounds. Drug Des. Devel. Ther. 16, 1067\u20131082 (2022).","journal-title":"Drug Des. Devel. Ther."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-25354-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-25354-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-25354-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T01:01:55Z","timestamp":1764378115000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-25354-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,24]]},"references-count":119,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["25354"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-25354-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,24]]},"assertion":[{"value":"11 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"41503"}}