[Paper] Elucidation of the inhibitory activity of ivermectin with host nuclear importin α and several SARS-CoV-2 targets

[-] TehCaster | 4 points | Apr 14 2021 21:58:26

Just posting in case DrBeen u/MastCell or whiteboard doctors or whoever watches this space :)

[-] mastcell | 4 points | Apr 15 2021 02:18:13

Thank you for sharing. I will check it out and possibly do a video.

It is becoming a little difficult as YouTube has categorically asked to not upload content that says that Ivermectin or HCQ can help with COVID.

[-] stereomatch | 2 points | Apr 16 2021 08:52:31

The paper is now available at Sci-Hub:

https://sci-hub.st/https://www.tandfonline.com/doi/full/10.1080/07391102.2020.1839564?src=recsys

[-] stereomatch | 2 points | Apr 15 2021 13:08:22

~~The full paper requires purchase - currently is not available on sci-hub. (enter the DOI reference given below on that website to get the pdf - although not available yet).~~

EDIT: The paper is now available at:

https://sci-hub.st/https://www.tandfonline.com/doi/full/10.1080/07391102.2020.1839564?src=recsys

3CLPro refers to "3 Chymotrypsin-like Protease" which is the protease that breaks up the large polyprotein into the required segments to make the proteins needed by the virus.

https://www.tandfonline.com/doi/abs/10.1080/07391102.2021.1911857 Elucidation of the inhibitory activity of ivermectin with host nuclear importin α and several SARS-CoV-2 targets

Martiniano Bello

Received 05 Feb 2021, Accepted 26 Mar 2021, Published online: 10 Apr 2021

https://doi.org/10.1080/07391102.2021.1911857

Abstract

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-α/β1 heterodimeric complex responsible for the translocation and replication of various viral species proteins. Also, IVM hampers SARS-CoV-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-α 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-α 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-α and Nsp9, which shared a similar relationship. Therefore, in vitro activity of IVM can be explained by acting as an inhibitor of importin-α, dimeric 3CLpro, and Nsp9, but mainly over dimeric 3CLpro.