{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:31:22Z","timestamp":1790775082315,"version":"4.1.0"},"reference-count":51,"publisher":"The Royal Society","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007446","name":"King Khalid University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007446","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020079","name":"Ramaiah Institute Of Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020079","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["R. Soc. Open Sci."],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:p>\n                    In this study, we have synthesized novel thiohydrazone\n                    <jats:bold>3(a\u2013b)<\/jats:bold>\n                    and hydrazone analogues\n                    <jats:bold>3(c)<\/jats:bold>\n                    by one-pot methodology with good to excellent yields (85%\u201391%).\n                    <jats:italic toggle=\"yes\">In silico<\/jats:italic>\n                    molecular dynamics (MD) simulations, docking, and absorption, distribution, metabolism, excretion and toxicity (ADMET) were evaluated as inhibitor activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PDB ID: 5N5O) main protease. The dynamics simulations studies and docking were conducted by GROMACS and AutoDock Vina. The ADMET studies of all the compounds were evaluated to understand drug-likeness and potential for therapeutic applications. All the synthesized compounds\n                    <jats:bold>3(a\u2013c)<\/jats:bold>\n                    exhibited strong docking scores between \u22125.0 and \u22125.4 kcal mol\n                    <jats:sup>\u22121<\/jats:sup>\n                    to the targeted protein. MD simulations revealed that the\n                    <jats:bold>3b<\/jats:bold>\n                    protein\u2013ligand complex demonstrated conformational stability throughout most of the 70 ns simulation period with root mean square deviation (RMSD) fluctuations below 3 \u00c5. ADMET predictions indicated that all compounds possessed high gastrointestinal absorption, suggesting good oral bioavailability. By slow evaporation technique, crystals of compound\n                    <jats:bold>3b<\/jats:bold>\n                    were grown using ethanol and its single crystal X-ray diffraction analysis disclosed that it crystallized in the monoclinic (P2\n                    <jats:sub>1<\/jats:sub>\n                    \/c) crystal system. Crystal data outlined crystal packing, bond lengths, bond angles, intermolecular hydrogen bonding parameters, etc. This study offers further avenues in the discovery of novel and promising hydrazone analogues against SARS-CoV-2 main protease.\n                  <\/jats:p>","DOI":"10.1098\/rsos.250373","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T12:29:52Z","timestamp":1752064192000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Design, synthesis, crystal structure of novel hydrazone analogues as SARS-CoV-2 potent inhibitors: MD simulations, MM-GBSA, docking and ADMET studies"],"prefix":"10.1098","volume":"12","author":[{"given":"C. R.","family":"Santhosh","sequence":"first","affiliation":[{"name":"Department of Chemistry, M.S. Ramaiah Institute of Technology (Affiliated to Visvesvaraya Technological University, Belgaum), Bengaluru, Karnataka 560054, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5334-9076","authenticated-orcid":true,"given":"Sampath","family":"Chinnam","sequence":"additional","affiliation":[{"name":"Department of Chemistry, M.S. Ramaiah Institute of Technology (Affiliated to Visvesvaraya Technological University, Belgaum), Bengaluru, Karnataka 560054, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guddekoppa S.","family":"Ananthnag","sequence":"additional","affiliation":[{"name":"Department of Chemistry and BSN Center for Nanomaterials and Display, B.M.S. College of Engineering, Bull Temple Road, Bengaluru, Karnataka 560019, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gbolahan O.","family":"Oduselu","sequence":"additional","affiliation":[{"name":"West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra P.O. Box LG 54, Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumarappan","family":"Chidambaram","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Asir Province 61421, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagaraju","family":"Kerru","sequence":"additional","affiliation":[{"name":"Department of Chemistry, GITAM School of Sciences, GITAM University, Bengaluru, Karnataka 561203, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagaraju","family":"Kottam","sequence":"additional","affiliation":[{"name":"Department of Chemistry, M.S. Ramaiah Institute of Technology (Affiliated to Visvesvaraya Technological University, Belgaum), Bengaluru, Karnataka 560054, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. M.","family":"Madhu","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, M.S. Ramaiah Institute of Technology (Affiliated to Visvesvaraya Technological University, Belgaum), Bengaluru, Karnataka 560054, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-023-00672-y"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.28732"},{"key":"e_1_3_8_4_2","first-page":"90","article-title":"Antivirals for COVID-19: a critical review","volume":"9","author":"Frediansyah A","year":"2021","unstructured":"Frediansyah A, Tiwari R, Sharun K, Dhama K, Harapan H. 2021 Antivirals for COVID-19: a critical review. CEGH 9, 90\u201398. (doi:10.1016\/j.cegh.2020.07.006))","journal-title":"CEGH"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2020.03.022"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/jocn.16150"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.14357"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25020739"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-022-00852-9"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/MS9.0000000000000839"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.4103\/0975-7406.129170"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.14590"},{"key":"e_1_3_8_13_2","doi-asserted-by":"publisher","DOI":"10.1039\/D3NJ03598K"},{"key":"e_1_3_8_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11164-023-05116-1"},{"key":"e_1_3_8_15_2","doi-asserted-by":"publisher","DOI":"10.4314\/tjpr.v22i1.17"},{"key":"e_1_3_8_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202400583"},{"key":"e_1_3_8_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2024.138634"},{"key":"e_1_3_8_18_2","doi-asserted-by":"crossref","DOI":"10.1128\/aac.01643-23","article-title":"Novel hydrazone compounds with broad-spectrum antiplasmodial activity and synergistic interactions with antimalarial drugs","volume":"68","author":"Rosado-Qui\u00f1ones AM","year":"2024","unstructured":"Rosado-Qui\u00f1ones AM et al. 2024 Novel hydrazone compounds with broad-spectrum antiplasmodial activity and synergistic interactions with antimalarial drugs. Antimicrob. Agents Chemother. 68, e0164323. (doi:10.1128\/aac.01643-23)","journal-title":"Antimicrob. Agents Chemother."},{"key":"e_1_3_8_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2023.135163"},{"key":"e_1_3_8_20_2","article-title":"Recent advances in anti-tuberculosis drug discovery based on hydrazide\u2013hydrazone and thiadiazole derivatives targeting InhA","volume":"16","author":"Teneva Y","year":"2023","unstructured":"Teneva Y, Simeonova R, Valcheva V, Angelova VT. 2023 Recent advances in anti-tuberculosis drug discovery based on hydrazide\u2013hydrazone and thiadiazole derivatives targeting InhA. Pharm 16, 484. (doi:10.3390\/ph16040484))","journal-title":"Pharm"},{"key":"e_1_3_8_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202200886"},{"key":"e_1_3_8_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27238393"},{"key":"e_1_3_8_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.134005"},{"key":"e_1_3_8_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2024.129679"},{"key":"e_1_3_8_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2024.139016"},{"key":"e_1_3_8_26_2","doi-asserted-by":"publisher","DOI":"10.1080\/00268976.2024.2407538"},{"key":"e_1_3_8_27_2","doi-asserted-by":"publisher","DOI":"10.1080\/10406638.2022.2138922"},{"key":"e_1_3_8_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2023.134997"},{"key":"e_1_3_8_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.132865"},{"key":"e_1_3_8_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cplett.2021.138563"},{"key":"e_1_3_8_31_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27165303"},{"key":"e_1_3_8_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.132869"},{"key":"e_1_3_8_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0410237"},{"key":"e_1_3_8_34_2","doi-asserted-by":"publisher","DOI":"10.1039\/D5MD00114E"},{"key":"e_1_3_8_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab255"},{"key":"e_1_3_8_36_2","doi-asserted-by":"publisher","DOI":"10.31643\/2023\/6445.13"},{"key":"e_1_3_8_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.18584"},{"key":"e_1_3_8_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.softx.2015.06.001"},{"key":"e_1_3_8_39_2","doi-asserted-by":"publisher","DOI":"10.1107\/S2053229614024218"},{"key":"e_1_3_8_40_2","first-page":"83","article-title":"Employing hexahydroquinolines as PfCDPK4 inhibitors to combat malaria transmission: an advanced computational approach","volume":"17","author":"Oduselu GO","year":"2024","unstructured":"Oduselu GO, Elebiju OF, Ogunnupebi TA, Akash S, Ajani OO, Adebiyi E. 2024 Employing hexahydroquinolines as PfCDPK4 inhibitors to combat malaria transmission: an advanced computational approach. Adv. Appl. Bioinform. Chem. 17, 83\u2013105. (doi:10.2147\/AABC.S476404)","journal-title":"Adv. Appl. Bioinform. Chem."},{"key":"e_1_3_8_41_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867329666221004104430"},{"key":"e_1_3_8_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molliq.2022.118901"},{"key":"e_1_3_8_43_2","doi-asserted-by":"publisher","DOI":"10.1039\/D0RA06379G"},{"key":"e_1_3_8_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/s42269-020-00389-7"},{"key":"e_1_3_8_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00894-021-04800-6"},{"key":"e_1_3_8_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddtec.2004.11.007"},{"key":"e_1_3_8_47_2","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2023.1264824"},{"key":"e_1_3_8_48_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm901137j"},{"key":"e_1_3_8_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10870-009-9595-z"},{"key":"e_1_3_8_50_2","doi-asserted-by":"publisher","DOI":"10.1107\/S1600536806022604"},{"key":"e_1_3_8_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/hlca.201200400"},{"key":"e_1_3_8_52_2","doi-asserted-by":"crossref","unstructured":"Santhosh CR Chinnam S Ananthnag GS Oduselu GO Chidambaram K Kerru N et al. 2025 Supplementary material from: Design synthesis crystal structure of novel hydrazone analogs as SARS-CoV-2 potent inhibitors: MD simulations MM-GBSA docking and ADMET studies. FigShare. (doi:10.6084\/m9.figshare.c.7901453)","DOI":"10.1098\/rsos.250373"}],"container-title":["Royal Society Open Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsos.250373","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/full-xml\/10.1098\/rsos.250373","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsos.250373","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T13:06:11Z","timestamp":1753967171000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/doi\/10.1098\/rsos.250373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":51,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1098\/rsos.250373"],"URL":"https:\/\/doi.org\/10.1098\/rsos.250373","relation":{"has-review":[{"id-type":"doi","id":"10.1098\/RSOS.250373\/v4\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOS.250373\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOS.250373\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOS.250373\/v2\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOS.250373\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOS.250373\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOS.250373\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOS.250373\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOS.250373\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOS.250373\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOS.250373\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOS.250373\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOS.250373\/v4\/decision1","asserted-by":"object"}]},"ISSN":["2054-5703"],"issn-type":[{"value":"2054-5703","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"2025-02-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-07","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":".250373"}}