De novo design approaches targeting an envelope protein pocket to identify small molecules against dengue virus

Leal, Emilse Soledad; Adler, Natalia S.; Fernández, Gabriela Araceli; Gebhard, Leopoldo Germán; Battini, Leandro; Aucar, María Gabriela; Videla, M.; Monge, Marı́a Eugenia; Ríos, Alejandro Hernández de los; Dávila, John Acosta; Morell, María L.; Cordo, Sandra M.; Garcı́a, Cybele C.; Gamarnik, Andrea V.; Cavasotto, Claudio N.; Bollini, Mariela

doi:10.1016/j.ejmech.2019.111628

Cited by 23 publications

(16 citation statements)

References 40 publications

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“…However, the mechanism of the viral inhibition is still unclear, and studies on the mechanism are yet to be reported. Leal et al (2019) reported thirty novel heterocyclic compounds enclosing the pyrimidine core to suppress the DENV activity [ 141 ]. Out of the thirty compounds, a few of them 90 – 95 ( Table 14 ) displayed the maximum DENV inhibition .…”

Section: Nitrogen ( N ) - Conta...mentioning

confidence: 99%

Seeking heterocyclic scaffolds as antivirals against dengue virus

Aamna²,

Sahu³

et al. 2022

European Journal of Medicinal Chemistry

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Section: Nitrogen ( N ) - Conta...mentioning

confidence: 99%

Seeking heterocyclic scaffolds as antivirals against dengue virus

Aamna²,

Sahu³

et al. 2022

European Journal of Medicinal Chemistry

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“…In 2019, a set of novel compounds targeting DENV E protein was presented [66]. The de novo design followed by molecular dynamics optimization led to 40, which was the most potent compound of the series active against all four serotypes of DENV (DENV1-DENV4) with the EC 50 value of 0.87 µM; 0.85 µM; 0.56 µM; 2.5 µM against DENV1, DENV2, DENV3, DENV4, respectively, and CC 50 = 18.1 µM and a satisfactory in vitro pharmacokinetics profile with solubility in simulated gastric fluid 506 µg/mL and t 1/2 > 120 min.…”

Section: Anti-flavivirus Agentsmentioning

confidence: 99%

The Fellowship of Privileged Scaffolds—One Structure to Inhibit Them All

Skoreński

Sieńczyk

2021

Pharmaceuticals

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Over the past few years, the application of privileged structure has emerged as a powerful approach to the discovery of new biologically active molecules. Privileged structures are molecular scaffolds with binding properties to the range of different biological targets. Moreover, privileged structures typically exhibit good drug-like properties, thus assuring more drug-like properties of modified compound. Our main objective is to discuss the privileged structures used for the development of antiviral agents.

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“…al. (2019) constructed a compound library comprising novel compounds postulated to have the ability to bind to the hydrophobic pocket similar to the β-OG molecule using the ligand-growing program Biochemical and Organic Model Builder (BOMB) [115,116]. They identified the 2,4-pyrimidine scaffold as the best candidate to be further developed as one of the molecules displayed antiviral activity in the µM range.…”

Section: De Novo Ligand Design Targeting the Denv E Proteinmentioning

confidence: 99%

“…Therefore, other techniques such as molecular dynamics simulation should be incorporated into virtual screening to improve the efficiency of the screening. The incorporation of molecular dynamics was proven to be useful as the study incorporating molecular dynamics identified two of the most potent anti-DENV compounds 3e and 3h [116].…”

Section: De Novo Ligand Design Targeting the Denv E Proteinmentioning

confidence: 99%

Structure-Based Design of Antivirals against Envelope Glycoprotein of Dengue Virus

Anasir

Ramanathan

Poh

2020

Viruses

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Dengue virus (DENV) presents a significant threat to global public health with more than 500,000 hospitalizations and 25,000 deaths annually. Currently, there is no clinically approved antiviral drug to treat DENV infection. The envelope (E) glycoprotein of DENV is a promising target for drug discovery as the E protein is important for viral attachment and fusion. Understanding the structure and function of DENV E protein has led to the exploration of structure-based drug discovery of antiviral compounds and peptides against DENV infections. This review summarizes the structural information of the DENV E protein with regards to DENV attachment and fusion. The information enables the development of antiviral agents through structure-based approaches. In addition, this review compares the potency of antivirals targeting the E protein with the antivirals targeting DENV multifunctional enzymes, repurposed drugs and clinically approved antiviral drugs. None of the current DENV antiviral candidates possess potency similar to the approved antiviral drugs which indicates that more efforts and resources must be invested before an effective DENV drug materializes.

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De novo design approaches targeting an envelope protein pocket to identify small molecules against dengue virus

Cited by 23 publications

References 40 publications

Seeking heterocyclic scaffolds as antivirals against dengue virus

Seeking heterocyclic scaffolds as antivirals against dengue virus

The Fellowship of Privileged Scaffolds—One Structure to Inhibit Them All

Structure-Based Design of Antivirals against Envelope Glycoprotein of Dengue Virus

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