Computational Investigation of Novel pUL56 Ligands Using Docking and Molecular Dynamics with Preliminary Cytotoxicity Evaluation: An Early-Stage Study
= -10.7 kcal/mol). In silico toxicity prediction (ProTox 3.0) classified NL as having low toxicity (class 4, LD50 ≈ 1000 mg/kg), which was confirmed in vitro, where NL demonstrated 158-fold less toxic (CC50 = 2.69 mg/mL) in MRC-5 cells than letermovir (0.017 mg/mL). Molecular dynamics simulations over 500 ns revealed that the pUL56-NL complex forms a more thermodynamically stable interaction, with a lower calculated free energy of binding (MMGBSA: -40.89 ± 7.40 kcal/mol vs. -32.76 ± 4.96 kcal/mol) and a narrower free energy landscape. These results establish NL as a promising, low-cytotoxicity candidate with enhanced target engagement, warranting further investigation as a potential anti-HCMV therapeutic.
Authors
- A. V. Kolobov
- Artem M. Klabukov (ORCID: https://orcid.org/0000-0002-7922-508X)
- Анна А. Штро (ORCID: https://orcid.org/0000-0002-2295-1881)
- Sergey Shityakov (ORCID: https://orcid.org/0000-0002-6953-9771)
- Р. И. Байчурин (ORCID: https://orcid.org/0000-0002-2737-1448)
- Samson Olusegun Afolabi (ORCID: https://orcid.org/0000-0002-6174-5044)
- Ekaterina V. Skorb
Institutions
- ITMO University (RU)
- Sechenov University (RU)
- Herzen University (RU)
- Yaroslavl State Technical University (RU)
- Research Institute of Influenza (RU)
- Saint-Petersburg State University Information Technologies, Mechanic and Optics (RU)
Publication Details
- Journal
- Molecules
- Published
- 2026-04-17
- DOI
- https://doi.org/10.3390/molecules31081310
- Primary Topic
- Cytomegalovirus and herpesvirus research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministry of Science and Higher Education of the Russian Federation
- Fondation Schlumberger pour l’Education et la Recherche