Bixinoids Derived from Bixa orellana as a Potential Zika Virus Inhibitor Using Molecular Simulations. Antiviral Effect on the Zika Virus of Bixinoids

Abstract Zika fever is a viral infection of great relevance in public health, especially in tropic regions, in which there is a predominance of mosquitoes of the genus Aedes, vectors of the disease. Microcephaly in neonatal children and Guillain-Barré syndrome in adults can be caused by the action of the Zika virus (ZIKV). Non-structural proteins, such as NS2B, NS3 and NS5, are important pharmacological targets, due to their action in the life cycle. The absence of anti-Zika drugs raises new research, including prospecting for natural products. This work investigated the in silico antiviral activity of bixin and six other derived molecules against the Zika viral proteins NS2B-NS3 and NS5. The optimized structure was subjected to molecular docking to characterize the interaction between bixinoids and ZIKV non-structural proteins, where significant interactions were observed with amino acid residues in the catalytic site in each enzyme. These results suggest that bixin and ethyl bixin has the potential to interfere with the enzymatic activity of NS2B, NS3 and NS5, thus being an indication of being a promising anti-Zika agent.

Vasoactive intestinal peptide: a potential target for antiviral therapy / 生理学报

Viral infection is clinically common and some viral diseases, such as the ongoing global outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have high morbidity and mortality. However, most viral infections are currently lacking in specific therapeutic agents and effective prophylactic vaccines, due to inadequate response, increased rate of drug resistance and severe adverse side effects. Therefore, it is urgent to find new specific therapeutic targets for antiviral defense among which "peptide-based therapeutics" is an emerging field. Peptides may be promising antiviral drugs because of their high efficacy and low toxic side effects. Vasoactive intestinal peptide (VIP) is a prospective antiviral peptide. Since its successful isolation in 1970, VIP has been reported to be involved in infections of SARS-CoV-2, human immune deficiency virus (HIV), vesicular stomatitis virus (VSV), respiratory syncytial virus (RSV), Zika virus (ZIKV) and cytomegalovirus (CMV). Additionally, given that viral attacks sometimes cause severe complications due to overaction of inflammatory and immune responses, the potent anti-inflammatory and immunoregulator properties of VIP facilitate it to be a powerful and promising candidate. This review summarizes the role and mechanisms of VIP in all reported viral infections and suggests its clinical potential as an antiviral therapeutic target.

Inhibition of Brazilian ZIKV strain replication in primary human placental chorionic cells and cervical cells treated with nitazoxanide

ABSTRACT Zika virus (ZIKV) infection during pregnancy is associated with a congenital syndrome. Although the virus can be detected in human placental tissue and sexual transmission has been verified, it is not clear how the virus reaches the fetus. Despite the emerging severity caused by ZIKV infection, no specific prophylactic and/or therapeutic treatment is available. The aim of the present study was to evaluate the effectiveness antiviral of nitazoxanide (NTZ) in two important congenital transmission targets: (i) a primary culture of human placental chorionic cells, and (ii) human cervical epithelial cells (C33-A) infected with Brazilian ZIKV strain. Initially, NTZ activity was screened in ZIKV infected Vero cells under different treatment regimens with non-toxic drug concentrations for 48 h. Antiviral effect was found only when the treatment was carried out after the viral inoculum. A strong effect against the dengue virus serotype 2 (DENV-2) was also observed suggesting the possibility of treating other Flaviviruses. Additionally, it was shown that the treatment did not reduce the production of infectious viruses in insect cells (C6/36) infected with ZIKV, indicating that the activity of this drug is also related to host factors. Importantly, we demonstrated that NTZ treatment in chorionic and cervical cells caused a reduction of infected cells in a dose-dependent manner and decreased viral loads in up to 2 logs. Pre-clinical in vitro testing evidenced excellent therapeutic response of infected chorionic and cervical cells and point to future NTZ activity investigation in ZIKV congenital transmission models with the perspective of possible repurposing of NTZ to treat Zika fever, especially in pregnant women.

Infección por virus zika y embarazo: revisión / Zika virus infection and pregnancy: review

La fiebre Zica es una enfermedad viral transmitida por diferentes especies del mosquito Aedes, causado por el virus ZIKA (ZIKV), que es un flavivirus de la familia Flaviridae y el serocomplejo Spondweni. Fue identificado por primera vez en un mono rhesus centinela en la selva Zika de Uganda, durante una investigación de fiebre amarilla en 1947. Los principales síntomas incluyen: fiebre de bajo grado (>38,5), artritis, artralgias en manos y pies,eritema máculopapular que se extiende de la cara hacia el cuerpo, conjuntivitis bilateral no purulenta (no en todos los pacientes), linfadenopatías cervicales,astenia y cefalea. La mayoría de los casos son asintomáticos; por cada persona sintomática, hay 4 casos sin síntomas. El período de incubación es de 2 a 12 días. El ZIKA se transmite por la picadura de un mosquito infectado del género Aedes en las Américas: Aedes aegypti and A. albopictus. También se transmite por vía vertical, perinatal, semen,sangre y lesiones accidentales del personal de laboratorio. La enfermedad comparte características clínicas tanto con el Dengue como con la fiebre Chikungunya, pero los síntomas son menos severos que las dos anteriores. El Síndrome de Guillain-Barré, asociado con el ZIKV, fue identificado en la Polinesia francesa en el año 2014, y mas recientemente en Brasil, Salvador, Colombia, Martinica, Surinam y Venezuela. Una complicación preocupante, identificada por primera vez en Brasil es la asociación de ZIKV con microcefalia de recién nacidos, cuyas madres habían sufrido la enfermedad durante el embarazo, especialmente en el primer trimestre. La OMS, el 1º de febrero del 2016, lanzó una alerta internacional sobre el ZIKV y su asociación con microcefalia y el Sindrome de Guillain-Barré. El presente escrito revisa las manifestaciones clínicas del virus Zika durante el embarazo y la asociación con microcefalia y otras malformaciones congénitas en fetos y recién nacidos(AU)

Zika fever is a viral disease transmitted by different species of the Aedes mosquito, caused by the Zika virus (ZIKV), which is a flavivirus from the Flaviviridae family and Spondweni serocomplex. The virus was identified for the first time on a sentinel rhesus monkey at the Zika forest in Uganda, in the midst of a yellow fever investigation, in 1947. The principal symptoms of the disease include: low-grade fever (<38.5°C), arthritis/ arthralgiae, mainly on hands and feet, maculopapular rash which usually extends from face to body, bilateral non purulent conjunctivitis (not observed on all patients), cervical lymphadenopathy, non specific general symptoms as myalgia, asthenia and headaches. Most ZIKV infection cases are asymptomatic, for each symptomatic person there are 4 asymptomatic cases. Incubation period is from 2 to 12 days. ZIKV is transmitted through the bite of an infected mosquito from the Aedes genus in the Americas: Aedes aegypti and A. albopictus. It is also transmitted through vertical and perinatal transmission, semen, blood, and accidental injuries of laboratory personal. The disease shares clinic characteristics with both Dengue and Chikungunya fevers, but symptoms are less severe than the other two diseases; The Guillain ­ Barré syndrome associated with the ZIKV was identified in the French Polynesia in 2014, and more recently in Brazil, El Salvador, Colombia, Martinique, Surinam and Venezuela. A concerning complication, identified in the world for the first time in Brazil, is the association of the ZIKV with microcephaly on newborns whose mothers had suffered the disease during pregnancy, principally in their first trimester. The World Health Organization, on February 1st, 2016 released an international sanitary alert regarding the Zika virus and its association with microcephaly and the Guillain ­ Barré syndrome. The present document reviews the clinical manifestations of the Zika virus during pregnancy, and the association with microcephaly and other congenital malformations on fetuses and newborns(AU)