• español
    • English
    • português
  • English 
    • español
    • English
    • português
  • Login
View Item 
  •   Home
  • Productos de Investigación - Creación
  • Repositorio Documental COVID-19
  • Documentos científicos relacionados a la COVID-19
  • View Item
  •   Home
  • Productos de Investigación - Creación
  • Repositorio Documental COVID-19
  • Documentos científicos relacionados a la COVID-19
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.
RecursosRecursos de apoyo¿Cómo publicar?

Browse

All of ExpeditioCommunities & CollectionsBy Issue DateAuthorsTitlesSubjects
This CollectionBy Issue DateAuthorsTitlesSubjects

My Account

LoginRegister

Statistics

View Usage StatisticsView Google Analytics Statistics

Current status of antivirals and druggable targets of SARS CoV-2 and other human pathogenic coronaviruses

Thumbnail

Citación

       
Export: <XML METS>
View/Open
Ver portada (89.76Kb)
Date
2020
Author
Artese, Anna
Svicher, Valentina
Costa, Giosué
Salpini, Romina
Di Maio, Velia Chiara
Alkhatib, Mohammad
Ambrosio, Francesca Alessandra
Santoro, Maria Mercedes
Assaraf, Yehuda G.
Alcaro, Stefano
Ceccherini-Silberstein, Francesca
Metadata
Show full item record
Imagenes y Videos
Captura.PNG

Abstract
Coronaviridae is a peculiar viral family, with a very large RNA genome and characteristic appearance, endowed with remarkable tendency to transfer from animals to humans. Since the beginning of the 21st century, three highly transmissible and pathogenic coronaviruses have crossed the species barrier and caused deadly pneumonia, inflicting severe outbreaks and causing human health emergencies of inconceivable magnitude. Indeed, in the past two decades, two human coronaviruses emerged causing serious respiratory illness: severe acute respiratory syndrome coronavirus (SARS-CoV-1) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV), causing more than 10,000 cumulative cases, with mortality rates of 10% for SARS-CoV-1 and 34.4% for MERS-CoV. More recently, the severe acute respiratory syndrome coronavirus virus 2 (SARSCoV-2) has emerged in China and has been identified as the etiological agent of the recent COVID19 pandemic outbreak. It has rapidly spread throughout the world, causing nearly 22 million cases and ~ 770,000 deaths worldwide, with an estimated mortality rate of ~3.6%, hence posing serious challenges for adequate and effective prevention and treatment. Currently, with the exception of the nucleotide analogue prodrug remdesivir, and despite several efforts, there is no known specific, proven, pharmacological treatment capable of efficiently and rapidly inducing viral containment and clearance of SARS-CoV-2 infection as well as no broad-spectrum drug for other human pathogenic coronaviruses. Another confounding factor is the paucity of molecular information regarding the tendency of coronaviruses to acquire drug resistance, a gap that should be filled in order to optimize the efficacy of antiviral drugs. In this light, the present review provides a systematic update on the current knowledge of the marked global efforts towards the development of antiviral strategies aimed at coping with the infection sustained by SARS-CoV-2 and other human pathogenic coronaviruses, displaying drug resistance profiles. The attention has been focused on antiviral drugs mainly targeting viral protease, RNA polymerase and spike glycoprotein, that have been tested in vitro and/or in clinical trials as well as on promising compounds proven to be active against coronaviruses by an in silico drug repurposing approach. In this respect, novel insights on compounds, identified by structure-based virtual screening on the DrugBank database endowed by multi-targeting profile, are also reported. We specifically identified 14 promising compounds characterized by a good in silico binding affinity towards, at least, two of the four studied targets (viral and host proteins). Among which, ceftolozane and NADH showed the best multi-targeting profile, thus potentially reducing the emergence of resistant virus strains. We also focused on potentially novel pharmacological targets for the development of compounds with anti-pan coronavirus activity. Through the analysis of a large set of viral genomic sequences, the current review provides a comprehensive and specific map of conserved regions across human coronavirus proteins which are essential for virus replication and thus with no or very limited tendency to mutate. Hence, these represent key druggable targets for novel compounds against this virus family. In this respect, the identification of highly effective and innovative pharmacological strategies is of paramount importance for the treatment and/or prophylaxis of the current pandemic but potentially also for future and unavoidable outbreaks of human pathogenic coronaviruses.
Palabras clave
SARS-CoV-2; Coronavirus; Outbreaks; Antiviral agents; Antiviral resistance; Conservation; RNA polymerase; Protease; Spike; Nucleoside analogs; Protease inhibitors; Entry inhibitors
URI
http://hdl.handle.net/20.500.12010/12815
Link to resource
https://doi.org/10.1016/j.drup.2020.100721
Collections
  • Documentos científicos relacionados a la COVID-19 [2292]
Comments

Respuesta Comentario Repositorio Expeditio

Gracias por tomarse el tiempo para darnos su opinión.


Carrera 4 # 22-61 Teléfono: (+57 1) 242 7030 - 018000111022 Fax: (+57 1) 561 2107 Bogotá D.C., Colombia

Fundación Universitaria de Bogotá Jorge Tadeo Lozano | Vigilada Mineducación

Institución de educación superior privada, de utilidad común, sin ánimo de lucro y su carácter académico es el de Universidad.

Reconocimiento personería jurídica: Resolución 2613 del 14 de agosto de 1959 Minjusticia.

Institución de Educación Superior sujeta a inspección y vigilancia por el Ministerio de Educación Nacional.

 

Términos y condiciones | Políticas

 

 


Carrera 4 # 22-61 Teléfono: (+57 1) 242 7030 - 018000111022 Fax: (+57 1) 561 2107 Bogotá D.C., Colombia

Fundación Universitaria de Bogotá Jorge Tadeo Lozano | Vigilada Mineducación

Institución de educación superior privada, de utilidad común, sin ánimo de lucro y su carácter académico es el de Universidad.

Reconocimiento personería jurídica: Resolución 2613 del 14 de agosto de 1959 Minjusticia.

Institución de Educación Superior sujeta a inspección y vigilancia por el Ministerio de Educación Nacional.

 

Términos y condiciones | Políticas