Abstract
The identification of novel therapeutics against the pandemic SARS-CoV-2 infection is an indispensable new address of current scientific research. In the search for anti-SARS-CoV-2 agents as alternatives to the vaccine or immune therapeutics whose efficacy naturally degrades with the occurrence of new variants, the salts of Bi 3+ have been found to decrease the activity of the Zn 2+ -dependent non-structural protein 13 (nsp13) helicase, a key component of the SARS-CoV-2 molecular tool kit. Here, we present a multilevel computational investigation based on the articulation of DFT calculations, classical MD simulations, and MIF analyses, focused on the examination of the effects of Bi 3+ /Zn 2+ exchange on the structure and molecular interaction features of the nsp13 protein. Our calculations confirmed that Bi 3+ ions can replace Zn 2+ in the zinc-finger metal centers and cause slight but appreciable structural modifications in the zinc-binding domain of nsp13. Nevertheless, by employing an in-house-developed ATOMIF tool, we evidenced that such a Bi 3+ /Zn 2+ exchange may decrease the extension of a specific hydrophobic portion of nsp13, responsible for the interaction with the nsp12 protein. The present study provides for a detailed, atomistic insight into the potential anti-SARS-CoV-2 activity of Bi 3+ and, more generally, evidences the hampering of the nsp13-nsp12 interaction as a plausible therapeutic strategy.
【초록키워드】 Efficacy, pandemic, SARS-COV-2 infection, anti-SARS-CoV-2, variants, immune, MD simulations, Helicase, nsp13, Protein, Research, non-structural protein, molecular, therapeutic strategy, Evidence, Interaction, Anti-SARS-CoV-2 Activity, domain, hydrophobic, molecular interaction, extension, Modification, Effect, feature, decrease, nsp12 protein, Occurrence, responsible, classical, provide, the vaccine, analyses, evidenced, Ion, degrade, MIF, the SARS-CoV-2, 【제목키워드】 nsp13, the SARS-CoV-2,