Abstract
In COVID-19 patients, respiratory failure was reported due to damage to the respiratory centers of the brainstem. Molecular mimicry of three brainstem pre-Botzinger complex proteins (DAB1, AIFM and SURF1) was regarded as the underlying reason for respiratory failure and the autoimmune neurological sequelae. Of the three brainstem proteins mimicked by SARS CoV-2, corresponding sequences to two of the mimicry peptides were located in the N-protein of SARS CoV-2. N-protein is important for viral RNA synthesis and genome packaging. Here, we have used molecular modeling, docking and MD simulations to discern potential drugs which can inhibit molecular mimicry of DAB1 by SARS CoV-2 and also eliminate it by interfering in genome packaging. The binding site (drug target) for molecular docking was defined as the amino acid sequence extending from position 168-185 of the N-protein which was a SLiM region and also included the mimicry hexapeptide. Molecular docking after MD simulations was used to discern probable inhibitors of the drug-target from FDA-approved neurological drugs in the Broad Institute's Drug Repurposing Hub. Our results revealed that an anti-anxiety drug afobazole qualified the ADMET parameters, formed a stable complex with the drug-target and exhibited the highest binding energy (-88.21 kJ/mol). This suggests that afobazole can be repurposed against SARS CoV-2 for disrupting molecular mimicry of human DAB1 protein and also eliminate the etiopathological agent by interfering in viral genome packaging. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-025-00316-6.