Towards in silico design of targeted therapeutics
Identyfikator grantu: PT01224
Kierownik projektu: Adam Liwo
Realizatorzy:
- Nevena Ilieva
Uniwersytet Gdański
Wydział Chemii
Gdańsk
Data otwarcia: 2025-02-06
Planowana data zakończenia grantu: 2027-02-06
Streszczenie projektu
This project aims to explore the potential of peptide aptamers grafted onto cyclotide scaffolds as antiviral agents targeting SARS-CoV-2 proteins. Peptide aptamers, combinatorial sequences of 5-20 amino acids, belong to the fastest-growing class of therapeutics – protein-based bioactive agents. They are gaining attention as alternatives to traditional drugs due to their small size, stability, and reduced immunogenicity. However, their experimental development is costly and complex. Integrating in silico approaches like molecular modelling and AI-based methods and techniques is a promising approach to address this challenge.
Cyclotides, highly stable cyclic peptides, provide an ideal framework for grafting aptamers, enhancing their stability, cellular uptake, and efficacy. This project focuses on designing aptamers against SARS-CoV-2 ORF6 and NSP13, proteins essential for viral replication and immune evasion. By inhibiting these targets, we aim to restore host immune responses, offering a novel antiviral strategy.
Both all-atom and coarse-grain approaches will be employed, particularly exploring new UNRES functionalities for modeling dynamic disulfide bridges, crucial in cyclotide design. Simulating systems of up to one million atoms demands substantial computational resources, highlighting the project's complexity and innovation in antiviral therapy development.
Cyclotides, highly stable cyclic peptides, provide an ideal framework for grafting aptamers, enhancing their stability, cellular uptake, and efficacy. This project focuses on designing aptamers against SARS-CoV-2 ORF6 and NSP13, proteins essential for viral replication and immune evasion. By inhibiting these targets, we aim to restore host immune responses, offering a novel antiviral strategy.
Both all-atom and coarse-grain approaches will be employed, particularly exploring new UNRES functionalities for modeling dynamic disulfide bridges, crucial in cyclotide design. Simulating systems of up to one million atoms demands substantial computational resources, highlighting the project's complexity and innovation in antiviral therapy development.