SrasV1, PubMed, Checkpoint, bibRecord, 000E34

Design, synthesis and evaluation of a series of acyclic fleximer nucleoside analogues with anti-coronavirus activity.

Identifieur interne : 000E34 ( PubMed/Checkpoint ); précédent : 000E33; suivant : 000E35

Design, synthesis and evaluation of a series of acyclic fleximer nucleoside analogues with anti-coronavirus activity.

Auteurs : Hannah L. Peters [États-Unis] ; Dirk Jochmans [Belgique] ; Adriaan H. De Wilde [Pays-Bas] ; Clara C. Posthuma [Pays-Bas] ; Eric J. Snijder [Pays-Bas] ; Johan Neyts [Belgique] ; Katherine L. Seley-Radtke [États-Unis]

Source :

Bioorganic & medicinal chemistry letters [ 1464-3405 ] ; 2015.

RBID : pubmed:26048809

Descripteurs français

KwdFr :
- Aciclovir (analogues et dérivés), Aciclovir (pharmacologie), Animaux, Antiviraux (), Antiviraux (pharmacologie), Cellules Vero, Conception de médicament, Coronavirus (), Coronavirus (physiologie), Coronavirus du syndrome respiratoire du Moyen-Orient (), Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie), Coronavirus humain NL63 (), Coronavirus humain NL63 (physiologie), Humains, Infections à coronavirus (traitement médicamenteux), Nucléosides (), Nucléosides (pharmacologie), Réplication virale (), Virus du SRAS (), Virus du SRAS (physiologie).
MESH :
- analogues et dérivés : Aciclovir.
- pharmacologie : Aciclovir, Antiviraux, Nucléosides.
- physiologie : Coronavirus, Coronavirus du syndrome respiratoire du Moyen-Orient, Coronavirus humain NL63, Virus du SRAS.
- traitement médicamenteux : Infections à coronavirus.
- Animaux, Antiviraux, Cellules Vero, Conception de médicament, Coronavirus, Coronavirus du syndrome respiratoire du Moyen-Orient, Coronavirus humain NL63, Humains, Nucléosides, Réplication virale, Virus du SRAS.

English descriptors

KwdEn :
- Acyclovir (analogs & derivatives), Acyclovir (pharmacology), Animals, Antiviral Agents (chemistry), Antiviral Agents (pharmacology), Chlorocebus aethiops, Coronavirus (drug effects), Coronavirus (physiology), Coronavirus Infections (drug therapy), Coronavirus NL63, Human (drug effects), Coronavirus NL63, Human (physiology), Drug Design, Humans, Middle East Respiratory Syndrome Coronavirus (drug effects), Middle East Respiratory Syndrome Coronavirus (physiology), Nucleosides (chemistry), Nucleosides (pharmacology), SARS Virus (drug effects), SARS Virus (physiology), Vero Cells, Virus Replication (drug effects).
MESH :
- chemical , analogs & derivatives : Acyclovir.
- chemical , chemistry : Antiviral Agents, Nucleosides.
- chemical , pharmacology : Acyclovir, Antiviral Agents, Nucleosides.
- drug effects : Coronavirus, Coronavirus NL63, Human, Middle East Respiratory Syndrome Coronavirus, SARS Virus, Virus Replication.
- drug therapy : Coronavirus Infections.
- physiology : Coronavirus, Coronavirus NL63, Human, Middle East Respiratory Syndrome Coronavirus, SARS Virus.
- Animals, Chlorocebus aethiops, Drug Design, Humans, Vero Cells.

Abstract

A series of doubly flexible nucleoside analogues were designed based on the acyclic sugar scaffold of acyclovir and the flex-base moiety found in the fleximers. The target compounds were evaluated for their antiviral potential and found to inhibit several coronaviruses. Significantly, compound 2 displayed selective antiviral activity (CC50 >3× EC50) towards human coronavirus (HCoV)-NL63 and Middle East respiratory syndrome-coronavirus, but not severe acute respiratory syndrome-coronavirus. In the case of HCoV-NL63 the activity was highly promising with an EC50 <10 μM and a CC50 >100 μM. As such, these doubly flexible nucleoside analogues are viewed as a novel new class of drug candidates with potential for potent inhibition of coronaviruses.

DOI: 10.1016/j.bmcl.2015.05.039
PubMed: 26048809

Affiliations:

Links toward previous steps (curation, corpus...)

to stream PubMed, to step Corpus: 000E12
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Le document en format XML

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<front><div type="abstract" xml:lang="en">A series of doubly flexible nucleoside analogues were designed based on the acyclic sugar scaffold of acyclovir and the flex-base moiety found in the fleximers. The target compounds were evaluated for their antiviral potential and found to inhibit several coronaviruses. Significantly, compound 2 displayed selective antiviral activity (CC50 >3× EC50) towards human coronavirus (HCoV)-NL63 and Middle East respiratory syndrome-coronavirus, but not severe acute respiratory syndrome-coronavirus. In the case of HCoV-NL63 the activity was highly promising with an EC50 <10 μM and a CC50 >100 μM. As such, these doubly flexible nucleoside analogues are viewed as a novel new class of drug candidates with potential for potent inhibition of coronaviruses.</div>
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Design, synthesis and evaluation of a series of acyclic fleximer nucleoside analogues with anti-coronavirus activity.

Design, synthesis and evaluation of a series of acyclic fleximer nucleoside analogues with anti-coronavirus activity.

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