Design, Synthesis and Discovery of N,N’-Carbazoyl-aryl-urea Inhibitors of Zika NS5 Methyltransferase and Virus Replication

Daniele Castagnolo

doi:10.1002/cmdc.201900533

Design, Synthesis and Discovery of N,N’-Carbazoyl-aryl-urea Inhibitors of Zika NS5 Methyltransferase and Virus Replication

Daniele Castagnolo

Institute of Pharmaceutical Science

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

35 Downloads (Pure)

Abstract

The recent outbreaks of Zika virus (ZIKV) infection worldwide make the discovery of novel antivirals against flaviviruses a research priority. This work describes the identification of novel inhibitors of ZIKV through a structure-based virtual screening approach using the ZIKV NS5-MTase. A novel series of molecules with a carbazoyl-aryl-urea structure has been discovered and a library of analogues has been synthesized. The new compounds inhibit ZIKV MTase with IC ₅₀ between 23–48 μM. In addition, carbazoyl-aryl-ureas also proved to inhibit ZIKV replication activity at micromolar concentration.

Original language	English
Pages (from-to)	385-390
Number of pages	6
Journal	Chemmedchem
Volume	15
Issue number	4
DOIs	https://doi.org/10.1002/cmdc.201900533
Publication status	Published - 17 Feb 2020

Keywords

Zika
antiviral agents
flavivirus
methyltransferase
urea

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/cmdc.201900533

Final draft_0411Accepted author manuscript, 22 MB

Cite this

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title = "Design, Synthesis and Discovery of N,N{\textquoteright}-Carbazoyl-aryl-urea Inhibitors of Zika NS5 Methyltransferase and Virus Replication",

abstract = "The recent outbreaks of Zika virus (ZIKV) infection worldwide make the discovery of novel antivirals against flaviviruses a research priority. This work describes the identification of novel inhibitors of ZIKV through a structure-based virtual screening approach using the ZIKV NS5-MTase. A novel series of molecules with a carbazoyl-aryl-urea structure has been discovered and a library of analogues has been synthesized. The new compounds inhibit ZIKV MTase with IC 50 between 23–48 μM. In addition, carbazoyl-aryl-ureas also proved to inhibit ZIKV replication activity at micromolar concentration. ",

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N2 - The recent outbreaks of Zika virus (ZIKV) infection worldwide make the discovery of novel antivirals against flaviviruses a research priority. This work describes the identification of novel inhibitors of ZIKV through a structure-based virtual screening approach using the ZIKV NS5-MTase. A novel series of molecules with a carbazoyl-aryl-urea structure has been discovered and a library of analogues has been synthesized. The new compounds inhibit ZIKV MTase with IC 50 between 23–48 μM. In addition, carbazoyl-aryl-ureas also proved to inhibit ZIKV replication activity at micromolar concentration.

AB - The recent outbreaks of Zika virus (ZIKV) infection worldwide make the discovery of novel antivirals against flaviviruses a research priority. This work describes the identification of novel inhibitors of ZIKV through a structure-based virtual screening approach using the ZIKV NS5-MTase. A novel series of molecules with a carbazoyl-aryl-urea structure has been discovered and a library of analogues has been synthesized. The new compounds inhibit ZIKV MTase with IC 50 between 23–48 μM. In addition, carbazoyl-aryl-ureas also proved to inhibit ZIKV replication activity at micromolar concentration.

KW - Zika

KW - antiviral agents

KW - flavivirus

KW - methyltransferase

KW - urea

UR - https://www.scopus.com/pages/publications/85078073812

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DO - 10.1002/cmdc.201900533

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JO - Chemmedchem

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IS - 4

ER -

Design, Synthesis and Discovery of N,N’-Carbazoyl-aryl-urea Inhibitors of Zika NS5 Methyltransferase and Virus Replication

Abstract

Keywords

UN SDGs

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