Microscopic interactions between ivermectin and key human and viral proteins involved in SARS-CoV-2 infection

The identification of suitable chemical structures able to effectively bind to the human/viral proteins involved in the SARS-CoV-2 infection cycle is crucial to fight this pathogen. Here we conduct a systematic molecular simulation study with the aim to assess the interactions of ivermectin, an antiparasitic drug with broad-spectrum antiviral activity, with the human Angiotensin-Converting Enzyme 2 (ACE2), the viral 3CLpro and PLpro proteases, and the viral SARS Unique Domain (SUD). The drug/target interactions are fully characterized from a physico-chemical perspective by elucidating the nature of the interactions and by quantifying their duration. Results reveal some persistent non-covalent interaction modes with the considered protein targets spanning several hundreds of nanoseconds, suggesting that ivermectin possesses a privileged chemical structure that could serve as a lead compound for future drug design studies against the infection cycle of betacoronaviruses.