The coronavirus disease 2019 (COVID-19) has affected the lives of millions of people around the world. In an effort to develop therapeutic interventions and control the pandemic, scientists have isolated several neutralizing antibodies against SARS-CoV-2 from the vaccinated and convalescent individuals. These antibodies can be explored further to understand SARS-CoV-2 specific antigen-antibody interactions and biophysical parameters related to binding affinity, which can be utilized to engineer more potent antibodies for current and emerging SARS-CoV-2 variants. In this regard, we have developed a database, Ab-CoV, which contains manually curated experimental interaction profiles of 1963 coronavirus-related neutralizing antibodies. It contains more than 3200 datapoints on experimental binding affinity (KD), half maximal inhibitory concentration (IC50), and half maximal effective concentration (EC50). Our analysis of the spike protein–antibody interface delves into amino acid residue propensity, pair preference, and atomic interaction energy. Notably, Tyr residues containing contacts were found to be highly preferred and energetically favourable at the interface of spike protein–antibody complexes. Further, we developed a regression model to relate the experimental binding affinity for antibodies using structural features, which achieved a correlation of 0.93. Moreover, several mutations at the spike protein–antibody interface were identified, which may lead to immune escape (epitope residues) and improved affinity (paratope residues) in current/emerging variants. A machine learning model with 82% accuracy to predict the immune escape of SARS-CoV-2 mutations was developed. For in silico therapeutic development, antibody repurposing framework for COVID-19 was designed. Although RT-qPCR tests for detecting SARS-CoV-2 infection are highly accurate, their sensitivity may diminish due to the virus's rapid evolution and mutations in the viral genome. So, we designed primers specific for Omicron variant for accurate diagnosis of SARS-CoV-2. Overall, our work provides insights into spike protein–antibody interactions, structural parameters influencing binding affinity, mutational effects on binding affinity change and immune escape, antibody repurposing and variant specific primer design. These efforts aim to engineer more effective therapeutics to combat COVID-19 and potential future infections.