Sauvat, Allan
Ciccosanti, Fabiola
Colavita, Francesca
Di Rienzo, Martina
Castilletti, Concetta
Capobianchi, Maria Rosaria
Kepp, Oliver
Zitvogel, Laurence
Fimia, Gian Maria
Piacentini, Mauro
Kroemer, Guido
2020-09-18T16:06:56Z
2020-09-18T16:06:56Z
2020-08-19
2041-4889
https://www.nature.com/articles/s41419-020-02842-x
http://hdl.handle.net/20.500.12010/13457
11 páginas
application/pdf
eng
Cell Death & Disease
reponame:Expeditio Repositorio Institucional UJTL
instname:Universidad de Bogotá Jorge Tadeo Lozano
medicamentos que inhiben la replicación del SARS-CoV-2
epidemic of coronavirus disease
inhibitors of viral
On-target versus off-target effects of drugs inhibiting the replication of SARS-CoV-2
Artículo
Síndrome respiratorio agudo grave
COVID-19
SARS-CoV-2
Coronavirus
info:eu-repo/semantics/restrictedAccess
info:eu-repo/semantics/acceptedVersion
Acceso restringido
https://doi.org/10.1038/s41419-020-02842-x
The current epidemic of coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) calls for the development of inhibitors of viral replication. Here, we performed a bioinformatic analysis of published and purported SARS-CoV-2 antivirals including imatinib mesylate that we found to suppress SARS-CoV-2 replication on Vero E6 cells and that, according to the published literature on other coronaviruses is likely to act on-target, as a tyrosine kinase inhibitor. We identified a cluster of SARS-CoV-2 antivirals with characteristics of lysosomotropic agents, meaning that they are lipophilic weak bases capable of penetrating into cells. These agents include cepharentine, chloroquine, chlorpromazine, clemastine, cloperastine, emetine, hydroxychloroquine, haloperidol, ML240, PB28, ponatinib, siramesine, and zotatifin (eFT226) all of which are likely to inhibit SARS-CoV-2 replication by non-specific (off-target) effects, meaning that they probably do not act on their ‘official’ pharmacological targets, but rather interfere with viral replication through non-specific effects on acidophilic organelles including autophagosomes, endosomes, and lysosomes. Imatinib mesylate did not fall into this cluster. In conclusion, we propose a tentative classification of SARS-CoV-2 antivirals into specific (on-target) versus non-specific (off-target) agents based on their physicochemical characteristics.
http://purl.org/coar/resource_type/c_6501