{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:21:56Z","timestamp":1779888116396,"version":"3.53.1"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Nematode infections impose a significant health and economic burden, particularly as parasites develop resistance to existing treatments and evade host defenses. This study explores the efficacy of 48 paraherquamide analogs, a class of polycyclic spiro-oxindole alkaloids with unique structural features, as potential anthelmintic agents. Employing advanced computational methods, including molecular docking, MM-GBSA, and molecular dynamics simulations, we assessed the interaction of these analogs with the Ls-AchBP receptor, a model for nematode neurotransmission. Among the analogs studied, Paraherquamide K, Mangrovamide A, and Chrysogenamide A showed comparable docking and MM-GBSA scores to the native antagonist. Notably, their binding interactions exhibited slight distinction attributed to structural differences, such as the absence of a di-oxygenated 7-membered ring. Additionally, these analogs demonstrated robust binding stability in the molecular dynamic simulation studies and favorable pharmacokinetic properties in our in-silico ADME assessment. The insights gained from the study highlight the potential of these analogs as a basis for developing new therapeutics for nematode infections. The promising results from this computational analysis set the stage for subsequent <jats:italic>in-vivo<\/jats:italic> validations and pre-clinical studies, contributing to the arsenal against parasitic resistance.<\/jats:p>","DOI":"10.1371\/journal.pone.0312009","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T18:40:43Z","timestamp":1731004843000},"page":"e0312009","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Paraherquamides \u2013 A new hope and great expectations of anthelmintic agents: Computational studies"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6192-5213","authenticated-orcid":true,"given":"Anfal S.","family":"Aljahdali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelsattar M.","family":"Omar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamal A.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali M.","family":"Almalki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6858-7560","authenticated-orcid":true,"given":"Sabrin R. 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