Potential inhibition of SARS-CoV-2 infection and its mutation with the novel geldanamycin analogue: Ignaciomycin

Abstract

The impact of novel coronavirus (SARS-CoV-2) is very high; its mutant variants provide a higher transmission rate. Due to many mutations in the omicron-variant, it can evade previously available neutralizing antibodies. The inhibitory effect of the novel compound “Ignaciomycin” was investigated using various computational analyses against the RBD of the SARS-CoV-2 wild-type, Delta, and omicron-variants. Molecular docking revealed the potentially stable interaction of Ignaciomycin with an energy value of −8.65 kcal/mol for the omicron-variant. DFT and Hirshfeld surface calculations showed higher efficiency and reactivity with strong electrostatic potential values. In-silico toxicity studies revealed a significant drug-likeness score (7.5912) with non-toxic properties. MD simulation studies confirmed the stability of Ignaciomycin during ∼ 100 ns simulation. Covariance, PCA, and FEL analyses revealed significant fluctuations in residues and atom mobility in all variants based on the strong interaction of Ignaciomycin. Mutations in the Delta and omicron-variants increased the binding efficiency of the RBD of the SARS-CoV-2 S-glycoprotein with human ACE2. Ignaciomycin had high efficiency in interacting with mutated sites in the RBD, thereby blocking the interaction of the RBD with ACE2. Our findings provide a strong hypothesis for preclinical validation of Ignaciomycin as a potential drug against SARS-CoV-2 and its mutant variants.