Current status, challenges and perspectives in the development of vaccines against yellow fever, dengue, Zika and chikungunya viruses

Silva, José V.J.; Lopes, Thaísa Regina Rocha; Oliveira-Filho, Edmilson F.; Oliveira, Renato Antônio dos Santos; Durães-Carvalho, Ricardo; Gil, Laura Helena Vega Gonzales

doi:10.1016/j.actatropica.2018.03.009

Cited by 55 publications

(44 citation statements)

References 68 publications

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“…Prophylactic or therapeutic treatment for CHIKV infections is still not available on the market, and vector control measures do not provide the ultimate solution [4]. Although progress is being made in CHIKV vaccine and antiviral drug development [3,[5][6][7], we would still be poorly prepared in the face of a new CHIKV epidemic.…”

Section: Introductionmentioning

confidence: 99%

Suramin Inhibits Chikungunya Virus Replication by Interacting with Virions and Blocking the Early Steps of Infection

Albulescu

White-Scholten

Taş

et al. 2020

Viruses

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Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that can cause a debilitating disease that is primarily characterized by persistent joint pain. CHIKV has been emerging globally, while neither a vaccine nor antiviral medication is available. The anti-parasitic drug suramin was previously shown to inhibit CHIKV replication. In this study we aimed to obtain more detailed insight into its mechanism of action. We found that suramin interacts with virions and can inhibit virus binding to cells. It also appeared to inhibit post-attachment steps of the infection process, likely by preventing conformational changes of the envelope glycoproteins required for fusion and the progression of infection. Suramin-resistant CHIKV strains were selected and genotyping and reverse genetics experiments indicated that mutations in E2 were responsible for resistance. The substitutions N5R and H18Q were reverse engineered in the E2 glycoprotein in order to understand their role in resistance. The binding of suramin-resistant viruses with these two E2 mutations was inhibited by suramin like that of wild-type virus, but they appeared to be able to overcome the post-attachment inhibitory effect of suramin. Conversely, a virus with a G82R mutation in E2 (implicated in attenuation of vaccine strain 181/25), which renders it dependent on the interaction with heparan sulfate for entry, was more sensitive to suramin than wild-type virus. Using molecular modelling studies, we predicted the potential suramin binding sites on the mature spikes of the chikungunya virion. We conclude that suramin interferes with CHIKV entry by interacting with the E2 envelope protein, which inhibits attachment and also interferes with conformational changes required for fusion.

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Section: Introductionmentioning

confidence: 99%

Suramin Inhibits Chikungunya Virus Replication by Interacting with Virions and Blocking the Early Steps of Infection

Albulescu

White-Scholten

Taş

et al. 2020

Viruses

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“…In this sense, DENV continues to increase in tropical and subtropical regions of the world, whereas outbreaks of YFV in humans have been reported in Angola and some countries in South America. Moreover, the emergence of ZIKV, which is strongly associated with microcephaly in newborns, Guillain-Barre syndrome in adults and the ability to be transmitted sexually and through trans placental route, as well as the neurotropic behavior of WNV; making these viruses a latent threat to global health (Barrett, 2017 ; Valderrama et al, 2017 ; Salles et al, 2018 ; Silva et al, 2018 ; Talero-Gutiérrez et al, 2018 ). Although, there is an approved and effective vaccine for YFV, an effective vaccine or treatment for DENV and ZIKV have not been achieved yet (Barrett, 2017 ; Silva et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

The Role of Host Cholesterol During Flavivirus Infection

Osuna-Ramos

Reyes-Ruiz

Ángel

2018

Front. Cell. Infect. Microbiol.

121

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In recent years the emergence and resurgence of arboviruses have generated a global health alert. Among arboviruses, Dengue (DENV), Zika (ZIKV), Yellow Fever (YFV), and West Nile (WNV) virus, belong to the genus Flavivirus, cause high viremia and occasionally fatal clinical disease in humans. Given the genetic austerity of the virus, they depend on cellular factors and organelles to complete its replication. One of the cellular components required for flavivirus infection is cholesterol. Cholesterol is an abundant lipid in biomembranes of eukaryotes cells and is necessary to maintain the cellular homeostasis. Recently, it has been reported, that cholesterol is fundamental during flavivirus infection in both mammal and insect vector models. During infection with DENV, ZIKV, YFV, and WNV the modulation of levels of host-cholesterol facilitates viral entry, replicative complexes formation, assembly, egress, and control of the interferon type I response. This modulation involves changes in cholesterol uptake with the concomitant regulation of cholesterol receptors as well as changes in cholesterol synthesis related to important modifications in cellular metabolism pathways. In view of the flavivirus dependence of cholesterol and the lack of an effective anti-flaviviral treatment, this cellular lipid has been proposed as a therapeutic target to treat infection using FDA-approved cholesterol-lowering drugs. This review aims to address the dependence of cholesterol by flaviviruses as well as the basis for anti flaviviral therapy using drugs which target is cholesterol synthesis or uptake.

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“…Currently, there are still no safe and effective vaccines or medicines to prevent or treat all the arboviruses carried by these vectors, except for yellow fever {26, 27]. Thus, measures adopted to control these diseases must consist of actions to reduce vector circulation and, consequently, viral circulation [26,28]. However, the current methodologies for monitoring and controlling A. aegypti and A. albopictus are not fully effective, as evidenced by the increasing cases of the arbovirus transmitted by these mosquitoes, according to the Brazilian Ministry of Health disclosures [29].…”

Section: Introductionmentioning

confidence: 99%

New traps for the capture of Aedes aegypti (Linnaeus) and Aedes albopictus (Skuse) (Diptera: Culicidae) eggs and adults

Silva

et al. 2020

Preprint

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The control of arboviruses carried by Aedes aegypti (Linnaeus) and Aedes albopictus (Skuse) can be performed with tools that monitor and reduce the circulation of these vectors. Therefore, the efficiency of four types of traps in capturing A. aegypti and A. albopictus eggs and adults, with the biological product Vectobac WG®, was evaluated in the field. For this, 20 traps were installed in two locations, which were in the South (Londrina, Paraná) and North (Manaus, Amazonas) Regions of Brazil, from March to April 2017 and January to February 2018, respectively. The UELtrap-E and UELtrap-EA traps captured A. aegypti and A. albopictus eggs: 1703/1866 eggs in Londrina, and 10268/2149 eggs in Manaus, respectively, and presented high ovitraps positivity index (OPI) values (averages: 100%/100% in Londrina, and 100%/96% in Manaus, respectively); and high egg density index (EDI) values (averages: 68/75 in Londrina, and 411/89 in Manaus, respectively), so they had statistically superior efficiency to that of the CRtrap-E and CRtrap-EA traps in both regions, that captured less eggs and adults: 96/69 eggs in Londrina, and 1091/510 eggs in Manaus, respectively. Also presented lower OPI values (averages: 28%/4% in Londrina, and 88%/60% in Manaus, respectively); and lower EDI values (averages: 10.5/9 in Londrina, and 47/30 in Manaus, respectively). The capture ratios of Aedes adults in the UELtrap-EA and CRtrap-EA traps in Londrina and Manaus were 53.3%/29.5% and 0%/9.8%, respectively. UELtrap-E and UELtrap-EA can be adopted as efficient tools for Aedes monitoring due to their high sensitivity, low cost and ease of use.Author summaryAedes aegypti and Aedes albopictus are species of mosquitoes responsible for the transmission of several arboviruses that cause infections worldwide. However, there are still no effective and safe vaccines or medications to prevent or treat arboviruses transmitted by these vectors, except for yellow fever. Moreover, current methodologies for monitoring and controlling A. aegypti and A. albopictus are not fully effective, as evidenced by the increasing cases of the arbovirus transmitted by these mosquitoes or have incompatible costs with the socioeconomic conditions of a large number of people. Thus, the traps tested in this study can be used as more effective and economical tools for monitoring and controlling A. aegypti and A. albopictus, since they are made with low cost material and they showed high efficiency in the capture of eggs, evidenced by the high values of ovitraps positive index and eggs density index, besides that one of the models captured Aedes spp. adults in both regions where they were tested. Therefore, the traps have potential for reducing Aedes spp. eggs and adults in the environment and sensibility for determining the local infestation index, which can be reconciled with official government strategies for more accurate vector monitoring and control actions.

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Current status, challenges and perspectives in the development of vaccines against yellow fever, dengue, Zika and chikungunya viruses

Cited by 55 publications

References 68 publications

Suramin Inhibits Chikungunya Virus Replication by Interacting with Virions and Blocking the Early Steps of Infection

Suramin Inhibits Chikungunya Virus Replication by Interacting with Virions and Blocking the Early Steps of Infection

The Role of Host Cholesterol During Flavivirus Infection

New traps for the capture of Aedes aegypti (Linnaeus) and Aedes albopictus (Skuse) (Diptera: Culicidae) eggs and adults

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