Bioquímica quântica aplicada ao estudo de anticorpos neutralizantes do SARS-CoV-2 detalhamento de suas interações com a proteína spike e desenho racional de peptídeos miméticos com potencial para tratar variantes do SARS-CoV-2

Abstract

The COVID-19 is caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus that has spread quickly worldwide since it was first detected in China, in late December 2019. This disease caused a pandemic and, consequently, numerous health, economic, and social problems, motivating the carry out of many studies focused on developing vaccines and efficient treatments. The monoclonal antibodies (mAbs) administration to treatment of COVID-19 was emergency approved in the USA after clinical trials indicated restricted disease progression and complication. The non-susceptibility of the Omicron variant to most approved (emergency) antibodies over pandemic made regulatory agencies no longer recommend their administrations in many regions, although a new mAb, bebtelovimab, received the emergency use authorization recently after clinical trials appointed its neutralization efficacy against that variant. The non-competing pair of mAbs B38 and P2B-2F6 are inhibitors of a crucial contact to viral entry in human cells, the interaction between the spike protein’s Receptor-binding domain (RBD) and Angiotensin-converting enzyme (ACE2). In that study were applied classic simulations of molecular dynamics and quantum calculations aim detail the interactions between every chain of these antibodies and the RBD using the crystallographic data deposited in the protein data bank (PDB IDs 7BZ5 e 7BWJ). The results indicated the crucial regions and interactions for the binding affinities in contact interfaces of the complexes B38:RBD and P2B-2F6:RBD. The residues of each chain of B38 with the most significant energetic contribution were the following (in ascending order of energy interaction): GLN27, GLY28, and ASN92 on the light chain (LC), besides TYR33, SER53, and ILE28 on the heavy chain (HC). The three main residues of each chain of P2B-2F6 with regard to interaction energy were (in ascending order of interaction energy): ASN33, TYR32, and TYR34 on LC, and TYR27, ILE103, and SER31 on HC. Moreover, the quantum description deepened the understanding of the binding mechanisms responsible for mAbs's neutralizing capacity, allowing the rational design of cyclic mimetic peptides that can be potentially used to treatment of patients infected by the Omicron variant of SARS-CoV-2.