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J Biomol Struct Dyn . Computational insights into the inhibitory potential of cyclotides Psyle B and Psyle C against key surface proteins of avian i

tetano

Editor, Senior Moderator
J Biomol Struct Dyn


. 2026 Aug 21:1-20.
doi: 10.1080/07391102.2026.2717568. Online ahead of print.
Computational insights into the inhibitory potential of cyclotides Psyle B and Psyle C against key surface proteins of avian influenza H5N1

Sidra Altaf[SUP] 1 [/SUP], Kainat Sarwar[SUP] 2 [/SUP], Rao Zahid Abbas[SUP] 3 [/SUP], Mostafa A Abdel-Maksoud[SUP] 4 [/SUP], Salman Alrokayan[SUP] 4 [/SUP], Bushra Hafeez Kiani[SUP] 5 [/SUP]


Affiliations
Abstract

Avian influenza viruses (AIVs) are RNA viruses endemic to wild birds, with highly pathogenic strains such as H5N1 causing major outbreaks. Hemagglutinin (HA) and neuraminidase (NA) proteins are key mediators of viral entry and spread. Cyclotides, plant-derived peptides with stable structures and potent bioactivity, have emerged as novel antiviral candidates. This study explored cyclotide-based drug design against H5N1 using computational approaches. HA and NA protein sequences were retrieved from NCBI and their physicochemical properties analyzed using ProtParam. Cyclotides from CyBase were modeled and refined in PyMOL, followed by molecular docking via ClusPro. Binding energies were further assessed with molecular mechanics generalized born surface area, while toxicity was predicted using ToxinPred. Molecular dynamics simulations supported the stability analyses. Results revealed that Psyle B and Psyle C exhibited strong interactions with HA and NA. Psyle B achieved a docking score of -1001.3 kcal/mol, and Psyle C -1031.6 kcal/mol, both predicted as non-toxic. These findings highlight Psyle B and Psyle C as promising antiviral leads. Nonetheless, in vitro and in vivo validation remains essential to confirm their therapeutic potential.

Keywords: Avian influenza; Psyle B; Psyle C; antiviral drug discovery; cyclotides; hemagglutinin (HA); in silico analysis; molecular docking; neuraminidase (NA).

 
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