Nanovectorization of Ivermectin to avoid overdose of drugs

Abstract

Ivermectin is an antiparasitic drug that results in the death of the targeted parasites using several mechanical actions. While very well supported, it can induce in rare cases, adverse effects including coma and respiratory failure in case of overdose. This problem should be solved especially in an emergency situation. For instance, the first pandemic of the 21th century was officially declared in early 2020, and while several vaccines around the worlds have been used, an effective treatment against this new strain of coronavirus, better known as SARS-CoV-2, should also be considered, especially given the massive appearance of variants. From all the tested therapies, Ivermectin showed a potential reduction of the viral portability, but sparked significant debate around the dose needed to achieve these positive results. To answer this general question, we propose, using simulations, to show that the nanovectorization of Ivermectin on BN oxide nanosheets can increase the transfer of the drug to its target and thus decrease the quantity of drug necessary to cope with the disease. This first application could help science to develop such nanocargo to avoid adverse effects.

Communicated by Ramaswamy H. Sarma

Keywords:

• Boron nitride oxide
• Ivermectin
• SARS-CoV-2
• molecular dynamics
• drug delivery

Acknowledgements

DFT calculations in vacuum and PCM, and MD simulations were performed at the supercomputer regional facility Mesocentre of the University of Franche-Comté onto 120 cpu with the assistance of K. Mazouzi. This work was granted access to the HPC resources of IDRIS, Jean Zay supercomputer, under the allocation 2020—DARI AP010711661 made by GENCI for another part of the MD simulations. We would like to express our gratitude to the IDRIS team (S. Requena, P.-F. Lavallée, R. Lacroix and S. Van Crienkingen), which was able to be very reactive to our request in a very tense pandemic climate, without whom this work would not have been possible. The authors thank the Communaute d’Agglomeration du Pays de Montbeliard (convention PMA-UFC).

Credit authors’ statement

Eric Duverger: Conceptualization, DFT Software, Original draft preparation Guillaume Herlem: Conceptualization, Supervision, Reviewing. Fabien Picaud: Conceptualization, MD Simulations, Supervision, Reviewing, Writing and Editing

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.