NS3 and NS5 Proteins: Important Targets for Anti-Dengue Drug Design

Teixeira

et al. 2017

Preprint

Abstract:Dengue virus (DENV) and chikungunya virus (CHIKV) are reemergent arboviruses that are transmitted by mosquitoes of the Aedes genus. During the last several decades, these viruses have been responsible for millions of cases of infection and thousands of deaths worldwide. Therefore, several investigations were conducted over the past few years to find antiviral compounds for the treatment of DENV and CHIKV infections. One attractive strategy is the screening of compounds that target enzymes involved in the replication of both DENV and CHIKV. In this review, we describe advances in the evaluation of natural products targeting the enzymes involved in the replication of these viruses.

Section: Ns3mentioning

confidence: 80%

Section: Ns5mentioning

confidence: 99%

Section: Ns5mentioning

confidence: 99%

Section: Structural Biology Of Denvmentioning

confidence: 99%

See 2 more Smart Citations

Potential Antivirals: Natural Products Targeting Replication Enzymes of Dengue and Chikungunya Viruses

Teixeira

et al. 2017

Preprint

“…Epitope or synthetic peptide based vaccines. As DENV has both structural and nonstructural proteins for its viral activity (Oliveira et al, 2014), conserved epitopes may prove to be useful in designing synthetic peptide based vaccine. This can be easily initiated in today's time, as there is no dearth of information about genome sequences in the databases (Hasan et al, 2013;Sharmin and Islam, 2014).…”

Section: Introductionmentioning

confidence: 99%

Highly conserved epitopes of DENV structural and non-structural proteins: Candidates for universal vaccine targets

Verma

Bhatnagar

Kumari

et al. 2019

Gene

A B S T R A C TDengue is a severe emerging arthropod borne viral disease occurring globally. Around two fifths of the world's population, or up to 3.9 billion people, are at a risk of dengue infection. Infection induces a life-long protective immunity to the homologous serotype but confers only partial and transient protection against subsequent infection caused by other serotypes. Thus, there is a need for a vaccine which is capable of providing a life-long protection against all the serotypes of dengue virus.In our study, comparative genomics of Dengue virus (DENV) was conducted to explore potential candidates for novel vaccine targets. From our analysis we successfully found 100% conserved epitopes in Envelope protein (RCPTQGE); NS3 (SAAQRRGR, PGTSGSPI); NS4A (QRTPQDNQL); NS4B (LQAKATREAQKRA) and NS5 proteins (QRGSGQV) in all DENV serotypes. Some serotype specific conserved motifs were also found in NS1, NS5, Capsid, PrM and Envelope proteins. Using comparative genomics and immunoinformatics approach, we could find conserved epitopes which can be explored as peptide vaccine candidates to combat dengue worldwide. Serotype specific epitopes can also be exploited for rapid diagnostics. All ten proteins are explored to find the conserved epitopes in DENV serotypes, thus making it the most extensively studied viral genome so far.

Aminopyrimidine Derivatives as Multiflavivirus Antiviral Compounds Identified from a Consensus Virtual Screening Approach

Serafim,

Kronenberger,

Rocha

et al. 2024

J. Chem. Inf. Model.

Around three billion people are at risk of infection by the dengue virus (DENV) and potentially other flaviviruses. Worldwide outbreaks of DENV, Zika virus (ZIKV), and yellow fever virus (YFV), the lack of antiviral drugs, and limitations on vaccine usage emphasize the need for novel antiviral research. Here, we propose a consensus virtual screening approach to discover potential protease inhibitors (NS3pro) against different flavivirus. We employed an in silico combination of a hologram quantitative structure–activity relationship (HQSAR) model and molecular docking on characterized binding sites followed by molecular dynamics (MD) simulations, which filtered a data set of 7.6 million compounds to 2,775 hits. Lastly, docking and MD simulations selected six final potential NS3pro inhibitors with stable interactions along the simulations. Five compounds had their antiviral activity confirmed against ZIKV, YFV, DENV-2, and DENV-3 (ranging from 4.21 ± 0.14 to 37.51 ± 0.8 μM), displaying aggregator characteristics for enzymatic inhibition against ZIKV NS3pro (ranging from 28 ± 7 to 70 ± 7 μM). Taken together, the compounds identified in this approach may contribute to the design of promising candidates to treat different flavivirus infections.