Instytut Podstawowych Problemów Techniki

UMO-2022/45/B/NZ1/02519

2023-01-03 / 2027-01-02

Jedyny wykonawca

NCN

OPUS

23

The proposed research will investigate the molecular biomechanics of the SARS-CoV-2 spike (S) protein and its interaction with human angiotensin-converting enzyme 2 (ACE2) receptor and several monoclonal antibodies (mAb) in the complex form considering several variant of concern (VoC). Our approach will combine experiments and simulations via Single Molecule Force Microscopy (SMFM), which is a unique technique to probe molecular forces and receptor–ligand interactions in real-time and molecular dynamics simulation. Our work aims at building the foundation of the molecular biomechanics in the adaptation/evolution of the SARS-CoV-2. SMFS technique does not have access to molecular details during virus-host cell attachment as well as the binding of antibodies on S protein. Such characterization will be only possible through the proposed research based on our novel approach. We aim to conduct exhaustive characterization for biomechanical parameters important for SARS-CoV-2 S VoCs attachment to host cell ACE2 receptor such as the mechanical stability of S/hACE2 and similar implication for immune evasion of variants in S/mAb complexes. Here we will consider the latest structural information deposited in the protein data bank. The primary hypothesis is that we will test is, whether the higher mechanical stability reported by us at the level of the receptor binding domain (RBD) in SARS-CoV-2 S protein has been fine-tuned by the emergence of new variants, increasing the strength of S/hACE2 binding and thus facilitating the spread of the disease in the world. Our approach will include the description of a viral cell membrane, which will provide a better representation of the typical S protein fluctuations under mechanical deformation.