COVID-19 causing SARS-CoV-2 virus’s spike protein investigation for
novel drug discovery and mutational impact analysis
Novel coronavirus (NCoV-19) also known as SARS CoV-2 is the emerging pathogen that reasoned for coronavirus disease 19 (COVID-19) associated causalities worldwide and continues doing so. Inhibition of the interaction of the receptor-binding domain (RBD) of the spike protein to the human angiotensin-converting enzyme (ACE 2) receptor is the most effective therapeutic formulation to restrict the contagious respiratory illness and multiple organ failure caused by SARS-CoV-2. Based on structure decoding of the RBD domain of spike protein using machine learning and deep learning-based tools, our group has generated a new set of small molecules, which have strong inhibiting properties on the binding of spike protein to ACE-2 receptors. The newly designed molecules showed better performance than several existing repurposing drugs. Conformational changes from closed to closed lock and open conformations of the SARS-CoV-2 binding to ACE 2 receptor were observed in presence of these small molecular inhibitors. Besides identifying the novel inhibitors against COVID-19, our group has recently investigated the high mutational potential of the interacting region of the SARS-CoV-2 virus with ACE2 receptor which is a growing concern among scientific communities and health professionals since it brings the effectiveness of repurposed drugs and vaccines for COVID-19 into question. In this latest work, we have identified 52 energetically favorable Spike mutations at the interface while binding to ACE2, of which only 36 significantly enhance the stabilization of the Spike-ACE2 complex. The stability order and molecular interactions of these mutations were also identified. The highest stabilizing mutation V503D confirmed in our study is also known for neutralization resistance.