Targeting Spike Protein: Modified Antibody for Broad-Spectrum Binding to Coronaviruses: An In Silico Study

Abstract

An antibody-mediated immune response against the Spike protein is one of the potential ways to target the SARS-CoV-2 virus. The discovery of a highly effective vaccine or an antiviral drug that specifically targets the viral entry or its replication pathway, are commonly pursued as a way to combat COVID-19-like situation. The SARS-CoV-2 virus has RNA as its genetic material, which is known for its high mutation rate. This makes the efficiency and efficacy of the vaccine against it suboptimal later due to the continuous mutations in the epitope region of the virus. This was evident in the case of the spread of the Omicron (B.1.1.529) variant. Here we tested an in-silico approach towards finding an antibody that has the potential to recognise and bind against the Spike protein of the virus across most of the variants. We achieved this by altering the sequences of the VDJ region in the heavy and light chains of the natural human antibody against the Spike protein of the SARS-CoV-2 virus (Wuhan, PDB ID: 7BWJ). This was one of the first antibodies to be studied and published along with a crystal structure during mid2020, and known to have the ability to bind and neutralize the Wuhan isolate. Iterative substitutions were induced in the 7BWJ antibody sequence in different combinations. After 28 iterations, a potential antibody was found to bind across the variants with a comparatively higher docking score. This antibody also showed the potential to target the Spike protein of many members of Coronaviruses.