Effect of Clinically Used Microtubule Targeting Drugs on Viral Infection and Transport Function
Microtubule targeting agents (MTAs) have been exploited mainly as anti-cancer drugs because of their impact on cellular division and angiogenesis. Additionally, microtubules (MTs) are key structures for intracellular transport, which is frequently hijacked during viral infection. We have analyzed the antiviral activity of clinically used MTAs in the infection of DNA and RNA viruses, including SARS-CoV-2, to find that MT destabilizer agents show a higher impact than stabilizers in the viral infections tested, and FDA-approved anti-helminthic benzimidazoles were among the most active compounds. In order to understand the reasons for the observed antiviral activity, we studied the impact of these compounds in motor proteins-mediated intracellular transport. To do so, we used labeled peptide tools, finding that clinically available MTAs impaired the movement linked to MT motors in living cells. However, their effect on viral infection lacked a clear correlation to their effect in motor-mediated transport, denoting the complex use of the cytoskeleton by viruses. Finally, we further delved into the molecular mechanism of action of Mebendazole by combining biochemical and structural studies to obtain crystallographic high-resolution information of the Mebendazole-tubulin complex, which provided insights into the mechanisms of differential toxicity between helminths and mammalians.
Main Authors: | Oliva, María A., Tosat-Bitrian, Carlota, Barrado-Gil, Lucía, Bonato, Francesca, Galindo, Inmaculada, Garaigorta, Urtzi, Álvarez-Bernad, Beatriz, París-Ogáyar, Rebeca, Lucena-Agell, Daniel, Giménez-Abián, Juan F., García-Dorival, Isabel, Urquiza, Jesús, Gastaminza, Pablo, Díaz, José Fernando, Palomo, Valle, Alonso, Covadonga |
---|---|
Other Authors: | Ministerio de Ciencia, Innovación y Universidades (España) |
Format: | artículo biblioteca |
Language: | English |
Published: |
Molecular Diversity Preservation International
2022-03-22
|
Subjects: | Antivirals, Microtubule targeting drugs, SARS-CoV-2, Mebendazole-tubulin complex crystal structure, |
Online Access: | http://hdl.handle.net/10261/269588 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100003339 http://dx.doi.org/10.13039/501100011033 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Similar Items
-
COVID-19: Drug targets and potential treatments
by: Gil, Carmen, et al.
Published: (2020-06-08) -
Antiviral drugs targeting endosomal membrane proteins inhibit distant animal and human pathogenic viruses
by: Galindo Estrada, Ignacio, et al.
Published: (2020-11-26) -
Ibuprofen, a traditional drug that may impact the course of COVID-19 new effective formulation in nebulizable solution
by: García Canclini, Néstor, et al.
Published: (2020-11) -
Antigens from the helminth Fasciola hepatica exert antiviral effects against SARS-CoV-2 in vitro
by: Serrat, Judit, et al.
Published: (2023) -
Identification of Niemann-Pick C1 protein as a potential novel SARS-CoV-2 intracellular target
by: García-Dorival, Isabel, et al.
Published: (2021-10)