Abstract: Journal of Biomolecular Structure and Dynamics ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/tbsd20 Elucidation of the inhibitory activity of ivermectin with host nuclear importin α and several SARSCoV-2 targets Martiniano Bello To cite this article: Martiniano Bello (2021): Elucidation of the inhibitory activity of ivermectin with host nuclear importin α and several SARS-CoV-2 targets, Journal of Biomolecular Structure and Dynamics, DOI: 10.1080/07391102.2021.1911857 To link to this article: https://doi.org/10.1080/07391102.2021.1911857 View supplementary material Published online: 10 Apr 2021. Submit your article to this journal Article views: 1920 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=tbsd20 JOURNAL OF BIOMOLECULAR STRUCTURE AND DYNAMICS https://doi.org/10.1080/07391102.2021.1911857 Elucidation of the inhibitory activity of ivermectin with host nuclear importin a and several SARS-CoV-2 targets Martiniano Bello ~o y Desarrollo de Nuevos Farmacos e Innovacion Biotecnologica de la Escuela Superior de Medicina, Instituto Laboratorio de Disen Politecnico Nacional, Ciudad de Mexico, Mexico Communicated by Ramaswamy H. Sarma ABSTRACT ARTICLE HISTORY Ivermectin (IVM) is an FDA-approved drug that has shown antiviral activity against a wide variety of viruses in recent years. IVM inhibits the formation of the importin-a/b1 heterodimeric complex responsible for the translocation and replication of various viral species proteins. Also, IVM hampers SARSCoV-2 replication in vitro; however, the molecular mechanism through which IVM inhibits SARS-CoV-2 is not well understood. Previous studies have explored the molecular mechanism through which IVM inhibits importin-a and several potential targets associated with COVID-19 by using docking approaches and MD simulations to corroborate the docked complexes. This study explores the energetic and structural properties through which IVM inhibits importin-a and five targets associated with COVID-19 by using docking and MD simulations combined with the molecular mechanics generalized Born surface area (MMGBSA) approach. Energetic and structural analysis showed that the main protease 3CLpro reached the most favorable affinity, followed by importin-a and Nsp9, which shared a similar relationship. Therefore, in vitro activity of IVM can be explained by acting as an inhibitor of importin-a, dimeric 3CLpro, and Nsp9, but mainly over dimeric 3CLpro. Received 5 February 2021 Accepted 26 March 2021