2026-10-12T04:57:27Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33867725 2026-09-16T17:54:19Z category_1 category_4 category_19 category_873 category_46 category_734 category_132 portal_5 item_type_3 month_year_09_2026

<p>Supporting files.</p> Muhammad Suleman (3829027) Imtiaz Ali (5366378) Abrar Mohammad Sayaf (11644294) Fakhrul Hassan (24998981) Usama Ilahi (22443762) Mohammed Alissa (16382572) Sergio Crovella (290351) Abdullah A. Shaito (18877114) Hadi M. Yassine (4675846) Biophysics Biochemistry Pharmacology Chemical Sciences not elsewhere classified Immunology Biological Sciences not elsewhere classified Infectious Diseases xlink "> alpha viral tegument protein unique long 21 underexplored therapeutic target thereby sustaining infection suppresses antiviral type stable interaction profiles persistent structural compactness host cyclic gmp herpes simplex virus facilitating viral replication evade host immunity employ multiple strategies mediated immune suppression south african natural mediated immune evasion total binding free favorable docking scores product scaffolds capable identified kaempferol 3 findings identify natural osw &# 8209 1 ul21 immune immune evasion docking scores binding free identify natural product scaffolds kaempferol 3 findings provide tier docking evasion function binding candidates product libraries &# 8722 ul21 remains ul21 n ul21 ), terminal domain study aimed soyasaponin ii signaling pathway <div><p>Alpha-herpesviruses, particularly herpes simplex virus type 1 (HSV-1), establish lifelong latency and employ multiple strategies to evade host immunity, thereby sustaining infection. A key mediator of this immune evasion is the viral tegument protein, unique long 21 (UL21), which disrupts the host cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway and suppresses antiviral type-I interferon responses, facilitating viral replication. Despite its important role in HSV-1 pathogenesis, UL21 remains an underexplored therapeutic target. This study aimed to identify natural-product scaffolds capable of targeting the UL21 N-terminal domain and potentially interfering with UL21-mediated immune evasion. Using comprehensive virtual screening of East and South African natural-product libraries, we employed a multi-tier computational workflow comprising molecular docking, molecular dynamics (MD) simulations, and binding free-energy calculations. Four compounds, Saundersioside C, kaempferol 3,7,4′-tri-O-β-glucoside, soyasaponin II, and OSW‑1, emerged as promising UL21-binding candidates with favorable docking scores and stable interaction profiles. Docking scores for saundersioside C, kaempferol 3,7,4′-tri-O-β-glucoside, soyasaponin II, and OSW-1 were −9.05, −8.94 kcal/mol, −7.45 kcal/mol, and −7.30 kcal/mol, respectively. Molecular dynamics (MD) trajectory analyses demonstrated stable conformational behavior as indicated by consistent root mean square deviation (RMSD), limited structural fluctuations, and persistent structural compactness. Total binding free-energy calculations further identified kaempferol 3,7,4′-tri-O-β-glucoside (−40.9 kcal/mol MM/GBSA; −33.9 kcal/mol MM/PBSA) as the compound with the most favorable predicted binding affinity toward UL21. Collectively, these findings identify natural-product scaffolds with high potential to modulate UL21-mediated immune suppression, with kaempferol 3,7,4′-tri-O-β-glucoside emerging as the most promising candidate. The findings provide a foundation for experimental validation and future antiviral drug development targeting HSV-1.</p></div> 2026-09-16T17:54:15Z Dataset Dataset 10.1371/journal.pone.0355499.s002 https://figshare.com/articles/dataset/_p_Supporting_files_p_/33867725 CC BY 4.0