{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T19:27:37Z","timestamp":1791833257706,"version":"4.3.4"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T00:00:00Z","timestamp":1699401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011821","name":"Ministry of Education \u2013 Kingdom of Saudi Arabi","doi-asserted-by":"publisher","award":["IFPIP: 1349-130-1443"],"award-info":[{"award-number":["IFPIP: 1349-130-1443"]}],"id":[{"id":"10.13039\/501100011821","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Tilapia Lake Virus (TiLV) is a disease that affects tilapia fish, causing a high rate of sudden death at any stage in their life cycle. Unfortunately, there are currently no effective antiviral drugs or vaccines to prevent or control the progression of this disease. Researchers have discovered that the CRM1 protein plays a critical function in the development and spreading of animal viruses. By inhibiting CRM1, the virus\u2019s spread in commercial fish farms can be suppressed. With this in mind, this study intended to identify potential antiviral drugs from two different tropical mangrove plants from tropical regions:\n                    <jats:italic>Heritiera fomes<\/jats:italic>\n                    and\n                    <jats:italic>Ceriops candolleana<\/jats:italic>\n                    . To identify promising compounds that target the CRM1 protein, a computer-aided drug discovery approach is employed containing molecular docking, ADME (absorption, distribution, metabolism and excretion) analysis, toxicity assessment as well as molecular dynamics (MD) simulation. To estimate binding affinities of all phytochemicals, molecular docking is used and the top three candidate compounds with the highest docking scores were selected, which are CID107876 (-8.3 Kcal\/mol), CID12795736 (-8.2 Kcal\/mol), and CID12303662 (-7.9 Kcal\/mol). We also evaluated the ADME and toxicity properties of these compounds. Finally, MD simulation was conducted to analyze the stability of the protein-ligand complex structures and confirm the suitability of these compounds. The computational study demonstrated that the phytochemicals found in\n                    <jats:italic>H<\/jats:italic>\n                    .\n                    <jats:italic>fomes<\/jats:italic>\n                    and\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>candolleana<\/jats:italic>\n                    could potentially serve as important inhibitors of TiLV, offering practical utility. However, further\n                    <jats:italic>in vivo<\/jats:italic>\n                    investigations are necessary to investigate and potentially confirm the effectiveness of these compounds as antiviral drugs against the virus TiLV.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0287944","type":"journal-article","created":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T13:40:15Z","timestamp":1699450815000},"page":"e0287944","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Identification of natural antiviral drug candidates against Tilapia Lake Virus: Computational drug design approaches"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6355-8314","authenticated-orcid":true,"given":"Md Afsar Ahmed","family":"Sumon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amer H.","family":"Asseri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Habibur Rahman","family":"Molla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Othman","family":"Aljahdali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Rifat","family":"Hasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Aminur","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Tawheed","family":"Hasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7151-6640","authenticated-orcid":true,"given":"Tofael Ahmed","family":"Sumon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Hosny","family":"Gabr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Shafiqul","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2985-1675","authenticated-orcid":true,"given":"Burhan","family":"Fakhurji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Moulay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Earl","family":"Larson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4578-3593","authenticated-orcid":true,"given":"Christopher L.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,11,8]]},"reference":[{"key":"pone.0287944.ref001","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1007\/s00484-022-02347-6","article-title":"Effect of environmental factors on growth performance of Nile tilapia (Oreochromis niloticus).","volume":"66","author":"ME Abd El-Hack","year":"2022","journal-title":"Int J Biometeorol"},{"key":"pone.0287944.ref002","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1111\/jfd.12650","article-title":"Detection of Tilapia Lake Virus in Egyptian fish farms experiencing high mortalities in 2015.","volume":"40","author":"P Nicholson","year":"2017","journal-title":"J Fish Dis."},{"key":"pone.0287944.ref003","doi-asserted-by":"crossref","first-page":"101665","DOI":"10.1016\/j.bcab.2020.101665","article-title":"Report on prevalence of tilapia lake virus infection in tilapia fishes (Oreochromis niloticus).","volume":"27","author":"SR Saranya","year":"2020","journal-title":"Biocatal Agric Biotechnol"},{"key":"pone.0287944.ref004","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1128\/CMR.00045-14","article-title":"Emerging and reemerging neglected tropical diseases: a review of key characteristics, risk factors, and the policy and innovation environment","volume":"27","author":"TK Mackey","year":"2014","journal-title":"Clin Microbiol Rev"},{"key":"pone.0287944.ref005","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.1128\/JCM.00827-14","article-title":"Identification of a novel RNA virus lethal to tilapia","volume":"52","author":"M Eyngor","year":"2014","journal-title":"J Clin Microbiol"},{"key":"pone.0287944.ref006","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.3389\/fmicb.2017.01171","article-title":"CRM1 inhibitors for antiviral therapy.","volume":"8","author":"C Mathew","year":"2017","journal-title":"Front Microbiol"},{"key":"pone.0287944.ref007","first-page":"139","article-title":"Hitting a moving target: inhibition of the nuclear export receptor XPO1\/CRM1 as a therapeutic approach in cancer.","volume":"1","author":"M Sendino","year":"2018","journal-title":"Cancer Drug Resist."},{"key":"pone.0287944.ref008","first-page":"48","article-title":"Verdinexor targeting of CRM1 is a promising therapeutic approach against RSV and Influenza viruses.","volume":"10","author":"JA Pickens","year":"2018","journal-title":"Viruses 2018, Vol 10, Page 48."},{"key":"pone.0287944.ref009","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1074\/mcp.M112.024877","article-title":"Identification of CRM1-dependent nuclear export cargos using quantitative mass spectrometry","volume":"12","author":"K Thakar","year":"2013","journal-title":"Mol Cell Proteomics"},{"key":"pone.0287944.ref010","doi-asserted-by":"crossref","first-page":"102346","DOI":"10.1016\/j.jksus.2022.102346","article-title":"Identification of phytochemical compounds to inhibit the matrix-like linker protein VP26 to block the assembles of white spot syndrome virus (WSSV) envelope and nucleocapsid protein of marine shrimp: In silico approach.","volume":"34","author":"MHR Molla","year":"2022","journal-title":"J King Saud Univ\u2014Sci"},{"key":"pone.0287944.ref011","doi-asserted-by":"crossref","first-page":"4838","DOI":"10.3390\/cimb44100329","article-title":"Pharmacophore-model-based virtual-screening approaches identified novel natural molecular candidates for treating human neuroblastoma","volume":"44","author":"FADM Opo","year":"2022","journal-title":"Curr Issues Mol Biol"},{"key":"pone.0287944.ref012","doi-asserted-by":"crossref","first-page":"4169","DOI":"10.3390\/molecules27134169","article-title":"Application of mathematical modeling and computational tools in the modern drug design and development process","volume":"27","author":"MR Hasan","year":"2022","journal-title":"Molecules"},{"key":"pone.0287944.ref013","article-title":"Immunoinformatics and computer-aided drug design as new approaches against emerging and re-emerging infectious diseases.","author":"MO Aljahdali","year":"2022","journal-title":"Antivir Drugs [Working Title]."},{"key":"pone.0287944.ref014","first-page":"27","article-title":"Computational identification of druggable bioactive compounds from Catharanthus roseus and Avicennia marina against colorectal cancer by targeting thymidylate synthase","author":"MR Islam","year":"2022","journal-title":"Molecules"},{"key":"pone.0287944.ref015","first-page":"253","article-title":"Compounds identified from marine mangrove plant (Avicennia alba) as potential antiviral drug candidates against WDSV, an in-silico Approach.","volume":"19","author":"MO Aljahdali","year":"2021","journal-title":"Mar Drugs 2021, Vol 19, Page 253."},{"key":"pone.0287944.ref016","doi-asserted-by":"crossref","unstructured":"Islam SI, Mou MJ, Sanjida S, Mahfuj S. Genetics of Aquatic Organisms 6(2), GA487 An In-silico approach for identifying phytochemical inhibitors against nervous necrosis virus (NNV) in Asian sea bass by targeting capsid protein. [cited 6 Dec 2022]. doi: 10.4194\/GA487","DOI":"10.4194\/GA487"},{"key":"pone.0287944.ref017","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2020.e05087","article-title":"Computational assessment of MCM2 transcriptional expression and identification of the prognostic biomarker for human breast cancer","volume":"6","author":"A Samad","year":"2020","journal-title":"Heliyon"},{"key":"pone.0287944.ref018","doi-asserted-by":"crossref","first-page":"186","DOI":"10.3390\/aquacj2020010","article-title":"Immunoinformatic Approaches to identify immune epitopes and design an epitope-based subunit vaccine against emerging Tilapia Lake Virus (TiLV).","volume":"2","author":"SI Islam","year":"2022","journal-title":"Aquac J"},{"key":"pone.0287944.ref019","first-page":"206995","article-title":"IMPPAT: A curated database of Indian medicinal plants, phytochemistry and therapeutics","author":"K Mohanraj","year":"2017","journal-title":"BioRxiv"},{"key":"pone.0287944.ref020","doi-asserted-by":"crossref","first-page":"103748","DOI":"10.1016\/j.sjbs.2023.103748","article-title":"Marine-derived sea urchin compounds as potential anti-cancer drug candidate against colorectal cancer: In silico and in vitro studies","volume":"30","author":"MHR Molla","year":"2023","journal-title":"Saudi J Biol Sci"},{"key":"pone.0287944.ref021","first-page":"6","article-title":"Structure prediction of transferrin receptor protein 1 (TfR1) by homology modelling, docking, and molecular dynamics simulation studies.","author":"MA AL-Refaei","year":"2020","journal-title":"Heliyon"},{"key":"pone.0287944.ref022","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1038\/nprot.2016.051","article-title":"Computational protein-ligand docking and virtual drug screening with the AutoDock suite.","volume":"11","author":"S Forli","year":"2016","journal-title":"Nat Protoc"},{"key":"pone.0287944.ref023","first-page":"8","article-title":"Predictive binding affinity of plant-derived natural products towards the Protein Kinase G enzyme of Mycobacterium tuberculosis (MtPknG).","author":"RM Qasaymeh","year":"2019","journal-title":"Plants."},{"key":"pone.0287944.ref024","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1517\/17460441.2010.484460","article-title":"Virtual screening with AutoDock: theory and practice.","volume":"5","author":"S Cosconati","year":"2010","journal-title":"Expert Opin Drug Discov."},{"key":"pone.0287944.ref025","first-page":"1","article-title":"SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"A Daina","year":"2017","journal-title":"Sci Reports 2017 71."},{"key":"pone.0287944.ref026","first-page":"10","article-title":"In silico toxicology: From structure\u2013activity relationships towards deep learning and adverse outcome pathways.","author":"J Hemmerich","year":"2020","journal-title":"Wiley Interdiscip Rev Comput Mol Sci"},{"key":"pone.0287944.ref027","first-page":"1","article-title":"Integrated structure model-based virtual screening approaches identified anti-cancer agents against prostate cancer by targeting MAOB protein","volume":"24","author":"M Habibur","year":"2023","journal-title":"Egypt J Med Hum Genet 2023 241."},{"key":"pone.0287944.ref028","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3390\/pr9010071","article-title":"Molecular dynamics simulations in drug discovery and pharmaceutical development","volume":"9","author":"OMH Salo-Ahen","year":"2021","journal-title":"process"},{"key":"pone.0287944.ref029","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/nrd2175","article-title":"Antiviral agents active against influenza A viruses","volume":"5","author":"E. De Clercq","year":"2006","journal-title":"Nat Rev Drug Discov"},{"key":"pone.0287944.ref030","first-page":"350","article-title":"Molecular docking and dynamics simulation analysis of thymoquinone and thymol compounds from Nigella sativa L.","volume":"16","author":"H Tabassum","year":"2020","journal-title":"that inhibits P38 protein: probable remedies for hepatocellular carcinoma. Med Chem"},{"key":"pone.0287944.ref031","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1007\/s11030-020-10151-w","article-title":"Molecular docking studies, molecular dynamics and ADME\/tox reveal therapeutic potentials of STOCK1N-69160 against papain-like protease of SARS-CoV-2","volume":"25","author":"OO Elekofehinti","year":"2021","journal-title":"Mol Divers"},{"key":"pone.0287944.ref032","first-page":"2021","article-title":"Identification of potential natural inhibitors of the receptor-binding domain of the SARS-CoV-2 spike protein using a computational docking approach.","author":"SM Mathew","year":"2021","journal-title":"Qatar Med J."},{"key":"pone.0287944.ref033","doi-asserted-by":"crossref","first-page":"e0155183","DOI":"10.1371\/journal.pone.0155183","article-title":"Vinardo: A Scoring function based on autodock vina improves scoring, docking, and virtual screening.","volume":"11","author":"R Quiroga","year":"2016","journal-title":"PLoS One."},{"key":"pone.0287944.ref034","doi-asserted-by":"crossref","first-page":"24048","DOI":"10.1021\/acsomega.2c00625","article-title":"Therapeutic potential of medicinal plants against dengue infection: a mechanistic viewpoint.","volume":"7","author":"M Altamish","year":"2022","journal-title":"ACS Omega"},{"key":"pone.0287944.ref035","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13321-018-0283-x","article-title":"ADMETlab: a platform for systematic ADMET evaluation based on a comprehensively collected ADMET database.","volume":"10","author":"J Dong","year":"2018","journal-title":"J Cheminform"},{"key":"pone.0287944.ref036","first-page":"12","article-title":"Bioinformatics approaches identified dasatinib and bortezomib inhibit the activity of MCM7 protein as a potential treatment against human cancer","author":"A Samad","year":"2022","journal-title":"Sci Rep"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0287944","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T13:40:54Z","timestamp":1699450854000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0287944"}},"subtitle":[],"editor":[{"given":"Abdulaziz","family":"Alouffi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,11,8]]},"references-count":36,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0287944","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.06.19.545628","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,8]]}}}