Antiviral Agents against Flavivirus Protease: Prospect and Future Direction

Samrat, Subodh Kumar; Xu, Jimin; Li, Zhong; Zhou, Jia; Li, Hongmin

doi:10.3390/pathogens11030293

Cited by 20 publications

(17 citation statements)

References 87 publications

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“…In 2016, the ZIKV was classified as a severe disease due to of its effects on newborns. , Most viruses in this family have similar structures; however, there is no specific drug to treat any of them. , Therefore, it is necessary to accelerate the methods of drug discovery and development. The traditional approach involves synthesizing compounds and testing them, which is a trial-and-error process. , The use of chemoinformatic techniques, such as the PTML method, can accelerate the discovery of potential drug candidates that can inhibit the development of this type of virus.…”

Section: Introductionmentioning

confidence: 99%

Implementation of IFPTML Computational Models in Drug Discovery Against Flaviviridae Family

Velásquez-López,

Ruiz-Escudero,

Arrasate

et al. 2024

J. Chem. Inf. Model.

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The Flaviviridae family consists of single-stranded positive-sense RNA viruses, which contains the genera Flavivirus, Hepacivirus, Pegivirus, and Pestivirus. Currently, there is an outbreak of viral diseases caused by this family affecting millions of people worldwide, leading to significant morbidity and mortality rates. Advances in computational chemistry have greatly facilitated the discovery of novel drugs and treatments for diseases associated with this family. Chemoinformatic techniques, such as the perturbation theory machine learning method, have played a crucial role in developing new approaches based on ML models that can effectively aid drug discovery. The IFPTML models have shown its capability to handle, classify, and process large data sets with high specificity. The results obtained from different models indicates that this methodology is proficient in processing the data, resulting in a reduction of the false positive rate by 4.25%, along with an accuracy of 83% and reliability of 92%. These values suggest that the model can serve as a computational tool in assisting drug discovery efforts and the development of new treatments against Flaviviridae family diseases.

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Section: Introductionmentioning

confidence: 99%

Implementation of IFPTML Computational Models in Drug Discovery Against Flaviviridae Family

Velásquez-López,

Ruiz-Escudero,

Arrasate

et al. 2024

J. Chem. Inf. Model.

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“…Highly conserved among flaviviruses, it is an essential enzyme in virus replication. Given its essential role, the NS2B/NS3 proteases (NS2B/NS3 pro ) of flaviviruses are promising drug targets; for example, DENV2, YFV, WNV, and ZIKV NS2B/NS3 pros present high amino acids sequence conservation and all four have the same structural fold, which confers a similar substrate specificity profile [ 16 , 17 ]. Due to their importance, we selected all four viruses to study the effect of a bioactive plant derivative molecule against NS2B/NS3 pro .…”

Section: Introductionmentioning

confidence: 99%

The Importance of Epigallocatechin as a Scaffold for Drug Development against Flaviviruses

et al. 2023

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Arboviruses such as Dengue, yellow fever, West Nile, and Zika are flaviviruses vector-borne RNA viruses transmitted biologically among vertebrate hosts by blood-taking vectors. Many flaviviruses are associated with neurological, viscerotropic, and hemorrhagic diseases, posing significant health and socioeconomic concerns as they adapt to new environments. Licensed drugs against them are currently unavailable, so searching for effective antiviral molecules is still necessary. Epigallocatechin molecules, a green tea polyphenol, have shown great virucidal potential against flaviviruses, including DENV, WNV, and ZIKV. The interaction of EGCG with the viral envelope protein and viral protease, mainly identified by computational studies, describes the interaction of these molecules with viral proteins; however, how the viral NS2B/NS3 protease interacts with epigallocatechin molecules is not yet fully deciphered. Consequently, we tested the antiviral potential of two epigallocatechin molecules (EGC and EGCG) and their derivative (AcEGCG) against DENV, YFV, WNV, and ZIKV NS2B/NS3 protease. Thus, we assayed the effect of the molecules and found that a mixture of the molecules EGC (competitive) and EGCG (noncompetitive) inhibited the virus protease of YFV, WNV, and ZIKV more effectively with IC50 values of 1.17 ± 0.2 µM, 0.58 ± 0.07 µM, and 0.57 ± 0.05 µM, respectively. As these molecules fundamentally differ in their inhibitory mode and chemical structure, our finding may open a new line for developing more effective allosteric/active site inhibitors to combat flaviviruses infection.

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“…Recently it was reported that niclosamide, an anthelminthic drug, which is historically used to treat tapeworm infection, could be repurposed for use against SARS-CoV-2 ( Garrett et al, 2021 ). Previously our lab was working on niclosamide and its derivatives as potent inhibitors against flaviviruses ( Li et al, 2020b ; Samrat et al, 2022 ; Xu et al, 2020c ). It has been shown that niclosamide suppressed the cytopathic effect (CPE) of SARS-CoV at a concentration of as low as 1 μM and inhibited SARS-CoV replication with an EC 50 value of less than 0.1 μM in Vero E6 cells ( Xu et al, 2020c ).…”

Section: Introductionmentioning

confidence: 99%