Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Molecular Docking and Molecular Dynamic Study of Two Viral Proteins Associated with SARS-CoV-2 with Ivermectin

Version 1 : Received: 17 April 2020 / Approved: 19 April 2020 / Online: 19 April 2020 (06:56:09 CEST)

How to cite: Gonzalez Paz, L.A.; Lossada, C.A.; Moncayo, L.S.; Romero, F.; Paz, J.L.; Vera-Villalobos, J.; Perez, A.E.; San-Blas, E.; Alvarado, Y.J. Molecular Docking and Molecular Dynamic Study of Two Viral Proteins Associated with SARS-CoV-2 with Ivermectin. Preprints 2020, 2020040334 (doi: 10.20944/preprints202004.0334.v1). Gonzalez Paz, L.A.; Lossada, C.A.; Moncayo, L.S.; Romero, F.; Paz, J.L.; Vera-Villalobos, J.; Perez, A.E.; San-Blas, E.; Alvarado, Y.J. Molecular Docking and Molecular Dynamic Study of Two Viral Proteins Associated with SARS-CoV-2 with Ivermectin. Preprints 2020, 2020040334 (doi: 10.20944/preprints202004.0334.v1).

Abstract

The global pandemic caused by the new SARS-COV-2 coronavirus makes it necessary to search for drugs for its control. Within of this research it has been known that the ivermectin drug, a FDA-approved drugs which is formulated as an 80:20 mixture of ivermectin B1a and B1b and used commonly for parasitic infections, has an inhibitory effect on viruses, includes SARS-COV-2 at in vitro level. In the particular case of SARS-COV-2 its mechanism of action remains elusive and controversial. Interestingly, the energy of interaction of ivermectin with any of the proteins the SARS-CoV-2 and the possible structural alterations at the protein level that this drug can cause have not been reported. In this sense, we carried out a bioinformatics study with docking strategies and molecular dynamics to predict the binding and disturbance induced by ivermectin in proteins associated with SARS-CoV-2. We use DockThor and Molegro docking scores. The DockThor server and myPresto software were used to build complexes and dynamics studies, respectively. The results obtained suggested that ivermectin is capable of docking with the 3CL protease and the HR2 domain, and may promote structural changes in these proteins by inducing unfolding/folding. Specifically, ivermectin brings protease to a significantly more deployed conformational state and the HR2 domain to a more compact state compared to the native state. Finally, it is shown that B1a and B1b macrocyclic lactones have a behavior different from to each target protein. These results suggest a possible inhibitory effect against SARS-CoV-2 due to a synergistic role of this drug to spontaneously bind to two important proteins involve in the proliferation of this virus. However, more studies are required on this possible mechanism of action.

Subject Areas

SARS-COV-2; folding/unfolding; antiparasitic; molecular docking; molecular dynamics; COVID-19; Ivermectin

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.