Development of a High-Throughput Antiviral Assay for Screening Inhibitors of Chikungunya Virus and Generation of Drug-Resistant Mutations in Cultured Cells

Gong, Edwin Yunhao; Bonfanti, Jean‐François; Ivens, Tania; Auwera, Marijke Van der; Kerckhove, Barbara Van; Kraus, Guenter

doi:10.1007/978-1-62703-484-5_32

Cited by 4 publications

(2 citation statements)

References 6 publications

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“…This obviously requires methodologies that can rapidly handle large numbers of individual tests. The use of a cell-based high-throughput ATP/luminescence screening assay is one approach that has been described to identify inhibitors of CHIKV (111). Using a 384-well-plate format, a liquid-dispensing system mixes cells with suspensions of compounds and the virus.…”

Section: High-throughput Screeningmentioning

confidence: 99%

Vaccine and Therapeutic Options To Control Chikungunya Virus

2018

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Beginning in 2004, chikungunya virus (CHIKV) went from an endemic pathogen limited to Africa and Asia that caused periodic outbreaks to a global pathogen. Given that outbreaks caused by CHIKV have continued and expanded, serious consideration must be given to identifying potential options for vaccines and therapeutics. Currently, there are no licensed products in this realm, and control relies completely on the use of personal protective measures and integrated vector control, which are only minimally effective. Therefore, it is prudent to urgently examine further possibilities for control. Vaccines have been shown to be highly effective against vector-borne diseases. However, as CHIKV is known to rapidly spread and generate high attack rates, therapeutics would also be highly valuable. Several candidates are currently being developed; this review describes the multiple options under consideration for future development and assesses their relative advantages and disadvantages.

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Section: High-throughput Screeningmentioning

confidence: 99%

Vaccine and Therapeutic Options To Control Chikungunya Virus

2018

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“…To be able to screen such large compound sets, antiviral evaluation need to be adapted to a high-throughput setting. The readout of the antiviral assay is often based on the inhibition of the virus-induced cytopathogenic effect (CPE) which can be measured by colorimetric methods (such as MTS, MTT) or by luminescence (ATPlite) [53,54]. Cells stably expressing a CHIKV replicon with a luciferase reporter have also been used in a high-throughput setup [46].…”

Section: 2-phenotypic Screening Of Compounds Of Natural or Synthetmentioning

confidence: 99%

Chikungunya virus drug discovery: still a long way to go?

Pérez‐Pérez

Priego

2019

Expert Opinion on Drug Discovery

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Introduction: Chikungunya virus (CHIKV) is the etiological agent of a (re)emerging arbovirus infection, chikungunya fever (CHIKF), that represents a serious health problem worldwide for which no antivirals are available. Areas covered: This review covers the efforts performed so far to identify and optimize small molecules that could be useful as antivirals for CHIKV infection, including drug repositioning, phenotypic screening, target-based screening and structure-based design. This is accompanied by a brief presentation of the replicative cycle of the virus and the role of the viral proteins in CHIKV replication. Expert opinion: In the last decade, and particularly since CHIKV reached the Americas, significant efforts have been made to identify compounds that effectively inhibit CHIKV replication. Unfortunately, these efforts have not led to a clinical candidate. For the years to come, more basic research is required to allow a better understanding of the interplay of the viral proteins among them and with cellular components. Structural information is missing for most of the targets so that structure-based drug design, a strategy that has provided good results in other antiviral fields, has been scarcely applied to this alphavirus.

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Antiviral drug discovery against arthritogenic alphaviruses: Tools and molecular targets

Abdelnabi

Jacobs

Neyts

2020

Biochemical Pharmacology

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Alphaviruses are (mainly) arthropod-borne viruses that belong to the family of the Togaviridae. Based on the disease they cause, alphaviruses are divided into an arthritogenic and an encephalitic group. Arthritogenic alphaviruses such as the chikungunya virus (CHIKV), the Ross River virus (RRV) and the Mayaro virus (MAYV) have become a serious public health concern in recent years. Epidemics are associated with high morbidity and the infections cause in many patients debilitating joint pain that can persist for months to years. The recent (2013-2014) introduction of CHIKV in the Americas resulted in millions of infected persons. Massive outbreaks of CHIKV and other arthritogenic alphaviruses are likely to occur in the future.Despite the worldwide (re-)emergence of these viruses, there are no antivirals or vaccines available for the treatment or prevention of infections with alphaviruses. It is therefore of utmost importance to develop antiviral strategies against these viruses. We here review the possible molecular targets in the replication cycle of these viruses for the development of antivirals. In addition, we provide an overview of the currently available in vitro systems and mouse infection models that can be used to assess the potential antiviral effect against these viruses.

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Development of a High-Throughput Antiviral Assay for Screening Inhibitors of Chikungunya Virus and Generation of Drug-Resistant Mutations in Cultured Cells

Cited by 4 publications

References 6 publications

Vaccine and Therapeutic Options To Control Chikungunya Virus

Vaccine and Therapeutic Options To Control Chikungunya Virus

Chikungunya virus drug discovery: still a long way to go?

Antiviral drug discovery against arthritogenic alphaviruses: Tools and molecular targets

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