1,3-Thiazolbenzamide Derivatives as Chikungunya Virus nsP2 Protease Inhibitors.
Larisa Ivanova,Kai Rausalu,Eva Žusinaite,Jaana Tammiku-Taul,Andres Merits,Mati Karelson +5 more
- Vol. 6, Iss: 8, pp 5786-5794
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TLDR
In this paper, two compounds 10 and 10c, identified by molecular docking, showed antiviral activity against CHIKV with IC50 of 13.1 and 8.3 μM, respectively.Abstract:
Chikungunya fever results from an infection with Chikungunya virus (CHIKV, genus Alphavirus) that is prevalent in tropical regions and is spreading fast to temperate climates with documented outbreaks in Europe and the Americas. Currently, there are no available vaccines or antiviral drugs for prevention or treatment of Chikungunya fever. The nonstructural proteins (nsPs) of CHIKV responsible for virus replication are promising targets for the development of new antivirals. This study was attempted to find out new potential inhibitors of CHIKV nsP2 protease using the ligand-based drug design. Two compounds 10 and 10c, identified by molecular docking, showed antiviral activity against CHIKV with IC50 of 13.1 and 8.3 μM, respectively. Both compounds demonstrated the ability to inhibit the activity of nsP2 in a cell-free assay, and the impact of compound 10 on virus replication was confirmed by western blot. The molecular dynamics study of the interactions of compounds 10 and 10c with CHIKV nsP2 showed that a possible mechanism of action of these compounds is the blocking of the active site and the catalytic dyad of nsP2.read more
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Anti-viral activity of thiazole derivatives: an updated patent review
TL;DR: This review covered reports in the patent literature in the period 2014 to the first quarter of 2021 on the antiviral activities of thiazole derivatives reported to inhibit a wide range of viruses including influenza viruses, coronaviruses, herpes viruses, hepatitis B and C, bovine viral diarrhea virus, chikungunya virus and human immunodeficiency viruses.
Journal ArticleDOI
In Silico Studies Revealed Interaction Mechanisms of Benzylidene-acrylohydrazide Derivates and nsP2 CHIKV
TL;DR: The chikungunya virus (CHIKV, Togaviridae family, Alphavirus genus) represents an emerging public health problem worldwide because it causes high morbidity and mortality rates.
Journal ArticleDOI
A review on structural genomics approach applied for drug discovery against three vector-borne viral diseases: Dengue, Chikungunya and Zika
TL;DR: The applications of the structural genomics approach towards the discovery of potential lead-like molecules against the genomic drug targets of three vector-borne diseases, namely, Dengue, Chikungunya and Zika are discussed.
Journal ArticleDOI
Discovery and optimization of natural-based nanomolar c-Kit inhibitors via in silico and in vitro studies.
TL;DR: Sarma et al. as discussed by the authors proposed a virtual screening of a library of natural-based compounds, which yielded three hits (2, 5 and 6) which possessed nanomolar inhibitory (2.02, 4.33 and 2.80) activity when tested in vitro against c-Kit.
Journal ArticleDOI
Design, synthesis, antiviral evaluation, and In silico studies of acrylamides targeting nsP2 from Chikungunya virus.
Shweta Choudhary,Gabriel Gomes Vilela,Gabriel Felipe Silva Passos,Clara Andrezza Crisóstomo Bezerra Costa,Johnnatan Duarte de Freitas,Grazielle Lobo Coelho,Júlia de Andrade Brandão,Leticia Anderson,Ênio José Bassi,João Xavier de Araújo-Júnior,Shailly Tomar,Edeildo Ferreira da Silva-Júnior +11 more
TL;DR: In this article , the authors used a rational drug design strategy to select some acrylamide derivatives to be synthesized and evaluated against CHIKV nsP2 and also screened on Chikungunya virus-infected cells.
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