Dengue, Zika Fever e Chikungunya: Aspectos Biológicos e Situação na América do Sul entre 2015 e 2020

Arboviroses são doenças causadas por vírus transmitidos por artrópodes e afetam as Américas, incluindo a América do Sul, onde provocam impactos na economia e na saúde pública. Entre os mais de 500 vírus registrados no Catálogo Internacional de Arbovírus, destacam-se os que causam dengue, febre zika e chikungunya. Assim, este artigo compreende um estudo descritivo baseado em dados secundários, onde são comparados aspectos biológicos e diagnósticos em relação a essas três enfermidades, bem como avaliamos sua presença, entre 2015 e 2020, nos países que integram a porção continental sul-americana. Apesar do considerável progresso feito nos últimos anos para melhor compreender os aspectos moleculares dos agentes etiológicos e das condições clínicas, o cenário é complexo e os três arbovírus causaram surtos na América do Sul, no período descrito, em proporções diferentes, e a dengue a mais comum, cujas taxas de incidência variam a cada ano analisado. O combate aos arbovírus deve ser permanente e requer políticas intersetoriais bem fundamentadas e responsabilidade individual. As intervenções governamentais precisam estreitar-se para implementar medidas de combate, e os sistemas de saúde e educação poderiam se alinhar de forma mais eficaz a fim de um trabalho mais forte de sensibilização que seja desencadeado desde os alunos da educação básica, auxiliando na educação continuada da população a favor da uma sociedade mais orientada e prudente. Também é necessário refletir sobre a eficácia dos sistemas de informações a fim de minimizar o problema da subnotificação, que impede de mostrar o real cenário dessas doenças.

Rift Valley Fever: a Threat to Pregnant Women Hiding in Plain Sight?

ABSTRACT The potential for emerging mosquito-borne viruses to cause fetal infection in pregnant women was overlooked until the Zika fever outbreak several years ago. Rift Valley fever virus (RVFV) is an emerging arbovirus with a long history of fetal infection and death in pregnant livestock. The effect of RVFV infection on pregnant women is not well understood. This Gem examines the effects that this important emerging pathogen has during pregnancy, its potential impact on pregnant women, and the current research efforts designed to understand and mitigate adverse effects of RVFV infection during pregnancy.

Pathophysiology of Zika Virus; From Infection to Cure

Zika virus is an icosahedral, enveloped, single-stranded RNA virus, a member of the family Flaviviridae, transmitted to humans by Aedes species mosquitoes. Unique features of Zika virus infection are sexual and transplacental transmission and associated neurological morbidities. The main objective of our review is to summarize the most of current information including epidemiology and pathophysiology of routes of transmission, prevalence, mode of infection, symptoms, diagnosis, treatment and vaccine strategies of Zika viral infection. This article is helpful to improve the treatment of Zika viral infection which will be beneficial for society. There are two different methods to diagnose the viral infection through RT-PCR and RNA NAT analysis. Vaccines have been developed against Zika virus, DNA vaccine effects actively than mRNA and live attenuated vaccines, due to its unique mode of infection. Treatment of Zika fever is supportive and primarily involves acetaminophen for fever, headache, or myalgia. ZIKV illness is generally mild in nature, requiring no specific treatment. As with treatment for dengue, nonsteroidal anti-inflammatory agents should be avoided if thrombocytopenia is present. The most successful trials are given by the DNA and mRNA vaccine which act by targeting the genome of the Zika virus or by inhibiting its protein synthesis mechanism.

Chloroquine and Sulfadoxine Derivatives Inhibit ZIKV Replication in Cervical Cells

Despite the severe morbidity caused by Zika fever, its specific treatment is still a challenge for public health. Several research groups have investigated the drug repurposing of chloroquine. However, the highly toxic side effect induced by chloroquine paves the way for the improvement of this drug for use in Zika fever clinics. Our aim is to evaluate the anti-Zika virus (ZIKV) effect of hybrid compounds derived from chloroquine and sulfadoxine antimalarial drugs. The antiviral activity of hybrid compounds (C-Sd1 to C-Sd7) was assessed in an in-vitro model of human cervical and Vero cell lines infected with a Brazilian (BR) ZIKV strain. First, we evaluated the cytotoxic effect on cultures treated with up to 200 µM of C-Sds and observed CC50 values that ranged from 112.0 ± 1.8 to >200 µM in cervical cells and 43.2 ± 0.4 to 143.0 ± 1.3 µM in Vero cells. Then, the cultures were ZIKV-infected and treated with up to 25 µM of C-Sds for 48 h. The treatment of cervical cells with C-Sds at 12 µM induced a reduction of 79.8% ± 4.2% to 90.7% ± 1.5% of ZIKV–envelope glycoprotein expression in infected cells as compared to 36.8% ± 2.9% of infection in vehicle control. The viral load was also investigated and revealed a reduction of 2- to 3-logs of ZIKV genome copies/mL in culture supernatants compared to 6.7 ± 0.7 × 108 copies/mL in vehicle control. The dose–response curve by plaque-forming reduction (PFR) in cervical cells revealed a potent dose-dependent activity of C-Sds in inhibiting ZIKV replication, with PFR above 50% and 90% at 6 and 12 µM, respectively, while 25 µM inhibited 100% of viral progeny. The treatment of Vero cells at 12 µM led to 100% PFR, confirming the C-Sds activity in another cell type. Regarding effective concentration in cervical cells, the EC50 values ranged from 3.2 ± 0.1 to 5.0 ± 0.2 µM, and the EC90 values ranged from 7.2 ± 0.1 to 11.6 ± 0.1 µM, with selectivity index above 40 for most C-Sds, showing a good therapeutic window. Here, our aim is to investigate the anti-ZIKV activity of new hybrid compounds that show highly potent efficacy as inhibitors of ZIKV in-vitro infection. However, further studies will be needed to investigate whether these new chemical structures can lead to the improvement of chloroquine antiviral activity.

Utilizing network pharmacology to explore the underlying mechanism of Cinnamomi Ramulus in Zika Fever induced by Zika Virus

Background: Zika fever is a mosquito-borne infection induced by Zika virus (ZIKV),effective drug and vaccine against ZIKV infection is still unavailable. Cinnamomi ramulus (CR) is a traditional Chinese herb with a long history ,can stimulate secretion of sweat and relieve exterior syndrome. The aim of this research was to evaluate the effect of CR against ZIKV and uncover its mechanism of action by network pharmacology.Methods: Cell viability assay, qRT-PCR assay and western blot assays were perfermed to evaluate anti-ZIKV activity in vitro. Survival rate, body weight were observed and viremia was detected in AG6 mice. Drug- target-disease networks, GO enrichment, and KEGG pathway analysis was established to clarify the therapeutic mechanismsits. Results: In this study, we find that CR can alleviate CPE after Zika virus infection. In the premixed administration mode, CR showed superior activity to inhibit viral RNA replication and protein expression in cells. Orally administered CR effectively protected AG6 mice infected with lethal doses of ZIKV, conferring 50% or 20% survival rate at a dosage of 900mg/ml or 450mg/ml, reducing body weight loss, inhibiting viral RNA replication. Beta-sitosterol, DBP, α-Longipinen, (-)-alpha-cedrene, ()-alpha-Longipinene may the main active compound and PTGS2, GABRA1, PTGS1, PTGES and CCR5 may the main targets. 176 biological processes, 16 cell components, 27 molecular functions, and 37 pathways were significantly identified in GO enrichment and pathway analysis. Conclusions: These results reveal that CR treatment of Zika fever is mainly related to PTGS1 and PTGS2 regulated prostaglandin release, metabolism, and inflammation response.