In Silico Analysis of Mutated SARS-CoV-2 N Protein of Java Origin and Human IgG Antibody as a Potential Vaccine Candidate

Abstract

The high mutation rate of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may alter viral protein structures and reduce the effectiveness of vaccines that primarily target the spike (S) protein. The nucleocapsid (N) protein is highly conserved and immunogenic, making it a promising alternative antigen for vaccine development. This study investigated the interaction and structural stability of the SARS-CoV-2 nucleocapsid proteins from three Indonesian variants (East Java, Central Java, and West Java) in complex with human immunoglobulin G (IgG) using in silico approaches. Three-dimensional structures were generated using I-TASSER, followed by protein–protein docking using ClusPro 2.0 and molecular dynamics simulations with GROMACS 2024.4 for 10 ns. Molecular docking showed that all nucleocapsid proteins interacted with human IgG through the complementarity-determining region (CDR). The wild type exhibited the highest binding affinity (ΔG = −12.5 kcal/mol), followed by the Central Java (−12.4 kcal/mol), East Java (−11.8 kcal/mol), and West Java (−11.5 kcal/mol) variants. Molecular dynamics analyses demonstrated that all antigen–antibody complexes remained structurally stable throughout the simulation. These findings suggest that the identified mutations had only a minor effect on binding affinity while maintaining stable antigen-antibody interactions, supporting the potential of the nucleocapsid protein as an alternative vaccine development.