Redesign computacional de anticorpos específicos para o domínio de ligação ao receptor (RBD) da proteína spike de SARS-CoV-2 com afinidade de ligação aumentada às sublinhagens ômicron

Abstract

The COVID-19 disease, despite vaccine efforts, is still responsible for a high number of cases and deaths worldwide. The emergence of new variants containing numerous mutations associated with greater transmissibility, infectivity and evasion of neutralizing antibodies represents the current great difficulty in limiting the spread of the disease. The aim of this study was to use computational protein design to redesign the CDRs of the CV30 antibody in order to increase the binding affinity of the antibody to the RBD of the Omicron sublineages of SARS-CoV-2. The results demonstrate that the redrawn antibodies, CV30 BA.4/5 and CV30 BA.5 BQ.1.1, showed a computationally higher binding affinity with the respective RBDs of the Omicron sublineages, with ΔG (Rosetta) binding of –56.8 REU and – 52.5 REU, respectively. The redesigned antibodies demonstrated greater changes in CDRH3 and light CDRs, compared to the antibody CV30. Furthermore, both antibodies showed increased interface area with the RBDs of the respective Omicron sublineages. The redesigned antibodies are promising candidates as neutralizing antibodies specific for the RBD of the BA.4/5 and BA.5 BQ.1.1 sublineages.