{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T19:07:15Z","timestamp":1768590435015,"version":"3.49.0"},"reference-count":56,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:00:00Z","timestamp":1690329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research at Imam Mohammad Ibn Saud Islamic University (IMSIU), Saudi Arabia","award":["RP-21-09-90"],"award-info":[{"award-number":["RP-21-09-90"]}]},{"name":"Deanship of Scientific Research at Imam Mohammad Ibn Saud Islamic University (IMSIU), Saudi Arabia","award":["NRF-2018-R1A6A1A03025124"],"award-info":[{"award-number":["NRF-2018-R1A6A1A03025124"]}]},{"name":"Core Research Institute (CRI) Program","award":["RP-21-09-90"],"award-info":[{"award-number":["RP-21-09-90"]}]},{"name":"Core Research Institute (CRI) Program","award":["NRF-2018-R1A6A1A03025124"],"award-info":[{"award-number":["NRF-2018-R1A6A1A03025124"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>The cell-traversal protein for ookinetes and sporozoites (CelTOS), expressed on the surface of ookinetes and sporozoitesin Plasmodium species, is a promising malaria vaccine candidate. CelTOS is essential for parasite invasion into mosquito midgut and human hepatocytes, thereby contributing to malaria transmission and disease pathogenesis. This study explores the genetic diversity, polymorphisms, haplotypes, natural selection, phylogenetic analysis, and epitope prediction in the full-length Plasmodium knowlesi CelTOS gene in clinical samples from Sarawak, Malaysian Borneo, and long-term laboratory strains from Peninsular Malaysia and the Philippines. Our analysis revealed a high level of genetic variation in the PkCelTOS gene, with a nucleotide diversity of \u03c0 ~ 0.021, which was skewed towards the 3\u2019 end of the gene. This level of diversity is double that observed in PfCelTOS and 20 times that observed in PvCelTOS from worldwide clinical samples. Tests of natural selection revealed evidence for positive selection within clinical samples. Phylogenetic analysis of the amino acid sequence of PkCelTOS revealed the presence of two distinct groups, although no geographical clustering was observed. Epitope prediction analysis identified two potential epitopes (96AQLKATA102 and 124TIKPPRIKED133) using the IEDB server and one epitope (125IKPPRIKED133) by Bcepred server on the C\u2019 terminal region of PkCelTOS protein. Both the servers predicted a common epitope region of nine amino acid length (IKPPRIKED) peptide, which can be studied in the future as a potential candidate for vaccine development. These findings shed light on the genetic diversity, polymorphism, haplotypes, and natural selection within PkCelTOS in clinical samples and provide insights about its future prospects as a potential candidate for P. knowlesi malaria vaccine development.<\/jats:p>","DOI":"10.3390\/tropicalmed8080380","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T01:09:01Z","timestamp":1690333741000},"page":"380","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["In Silico Analysis Reveals High Levels of Genetic Diversity of Plasmodium knowlesi Cell Traversal Protein for Ookinetes and Sporozoites (PkCelTOS) in Clinical Samples"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3407-7220","authenticated-orcid":false,"given":"Md Atique","family":"Ahmed","sequence":"first","affiliation":[{"name":"ICMR-Regional Medical Research Centre, NE Region, Dibrugarh 786010, Assam, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pratisthita","family":"Baruah","sequence":"additional","affiliation":[{"name":"ICMR-Regional Medical Research Centre, NE Region, Dibrugarh 786010, Assam, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9614-3238","authenticated-orcid":false,"given":"Ahmed","family":"Saif","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, King Khalid University, Abha 61321, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0836-6675","authenticated-orcid":false,"given":"Jin-Hee","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Al-Zharani","sequence":"additional","affiliation":[{"name":"Biology Department, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSU), Riyadh 11623, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syeda Wasfeea","family":"Wazid","sequence":"additional","affiliation":[{"name":"Arogyo Society of Health, Welfare and Support (ASHWAS), Guwahati 785640, Assam, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saad","family":"Alkahtani","sequence":"additional","affiliation":[{"name":"Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0651-2739","authenticated-orcid":false,"given":"Saurav J.","family":"Patgiri","sequence":"additional","affiliation":[{"name":"ICMR-Regional Medical Research Centre, NE Region, Dibrugarh 786010, Assam, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed S.","family":"Al-Eissa","sequence":"additional","affiliation":[{"name":"Biology Department, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSU), Riyadh 11623, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0419-9339","authenticated-orcid":false,"given":"Fu-Shi","family":"Quan","sequence":"additional","affiliation":[{"name":"Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Core Research Institute (CRI), Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,26]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2023, March 30). 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