SARS-CoV-2-induced phosphorylation and its pharmacotherapy backed by artificial intelligence and machine learning

Summary points Phosphorylation, involving phosphate group addition to viral and host proteins, influences SARS-CoV-2 pathogenicity. Study uses data mining to identify upregulated kinases responsible for proteomic changes induced by SARS-CoV-2. Spike and nucleocapsid protein sequences of SARS-CoV-2 were analyzed using predictive and structure-based tools. The tools categorized into groups such as protein structure analysis, consensus-based, homology-based, and supervised methods. Eight missense variants identified in viral sequences, with one potentially damaging variant. SNPs&Go and PolyPhen-2 predicted four distinct possibly damaging variants of SARS-COV-2. Promising therapeutic candidates include gilteritinib, pictilisib, sorafenib, RO5126766 and omipalisib. These compounds could mitigate SARS-CoV-2 virulence and pathogenicity by modulating phosphorylation pathways and addressing viral protein variants. The current study is not but a comprehensive analysis crucial to understanding disruptions in spike and nucleocapsid protein’s structure and function. MutPred2 uses a grouping-based machine learning model trained on positive-unlabeled data. MutPred2 demonstrates probabilities to interpret pathogenicity and mutation scores. Enhances understanding of genetic variations’ impact on protein structure and function. SNAP2 employs a neural network-based classifier with 848 input nodes, 25 hidden nodes and two output nodes (neutral and deleterious). The prediction analysis cover structural, functional, secondary structure, localization, transmembrane domains, catalytic functions, interactions, post-translational modifications, metal-binding and allosteric properties. Drugs and kinase inhibitors mapped to specific phosphorylation sites. Kinases and phosphatases are phospho-transferases, regulating cellular protein form and function. Human genome contains approximately 156 phosphatases and 568 protein kinases, involved in biological regulation. Dysregulation of kinases and phosphatases can have serious health consequences. Mutations in these enzymes can lead to disorders, and inhibitors are used as pharmacological tools. Protein Kinase Inhibitors (PKIs) and Phosphatase Inhibitors (PIs) are in experimental and clinical development, with various attributes and applications. The use of multiple methods increases prediction robustness in the research. Further investigation and experimental validation required to assess their efficacy as COVID-19 treatments.