ZIKV viral proteins and their roles in virus-host interactions

Guo, Moujian; Hui, Lixia; Nie, Yiwen; Tefsen, Boris; Wu, Ying

doi:10.1007/s11427-020-1818-4

Cited by 11 publications

(9 citation statements)

References 100 publications

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“…Some of the active extracts showed virucidal properties since their activity relied on direct inactivation of the viral particles before virus adsorption. It is also speculated that compounds in the crude extracts could interfere with the virion envelope, masking the E and M proteins necessary for viral adsorption and entry into the host cells [ 42 – 45 ]. However, the composition and the precise mechanism of action of the virucidal extracts identified in this study needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

Searching for plant-derived antivirals against dengue virus and Zika virus

Barbosa

Alves

Kohlhoff

et al. 2022

Virol J

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Background The worldwide epidemics of diseases as dengue and Zika have triggered an intense effort to repurpose drugs and search for novel antivirals to treat patients as no approved drugs for these diseases are currently available. Our aim was to screen plant-derived extracts to identify and isolate compounds with antiviral properties against dengue virus (DENV) and Zika virus (ZIKV). Methods Seven thousand plant extracts were screened in vitro for their antiviral properties against DENV-2 and ZIKV by their viral cytopathic effect reduction followed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, previously validated for this purpose. Selected extracts were submitted to bioactivity-guided fractionation using high- and ultrahigh-pressure liquid chromatography. In parallel, high-resolution mass spectrometric data (MSn) were collected from each fraction, allowing compounds into the active fractions to be tracked in subsequent fractionation procedures. The virucidal activity of extracts and compounds was assessed by using the plaque reduction assay. EC50 and CC50 were determined by dose response experiments, and the ratio (EC50/CC50) was used as a selectivity index (SI) to measure the antiviral vs. cytotoxic activity. Purified compounds were used in nuclear magnetic resonance spectroscopy to identify their chemical structures. Two compounds were associated in different proportions and submitted to bioassays against both viruses to investigate possible synergy. In silico prediction of the pharmacokinetic and toxicity (ADMET) properties of the antiviral compounds were calculated using the pkCSM platform. Results We detected antiviral activity against DENV-2 and ZIKV in 21 extracts obtained from 15 plant species. Hippeastrum (Amaryllidaceae) was the most represented genus, affording seven active extracts. Bioactivity-guided fractionation of several extracts led to the purification of lycorine, pretazettine, narciclasine, and narciclasine-4-O-β-D-xylopyranoside (NXP). Another 16 compounds were identified in active fractions. Association of lycorine and pretazettine did not improve their antiviral activity against DENV-2 and neither to ZIKV. ADMET prediction suggested that these four compounds may have a good metabolism and no mutagenic toxicity. Predicted oral absorption, distribution, and excretion parameters of lycorine and pretazettine indicate them as candidates to be tested in animal models. Conclusions Our results showed that plant extracts, especially those from the Hippeastrum genus, can be a valuable source of antiviral compounds against ZIKV and DENV-2. The majority of compounds identified have never been previously described for their activity against ZIKV and other viruses.

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Section: Discussionmentioning

confidence: 99%

Searching for plant-derived antivirals against dengue virus and Zika virus

Barbosa

Alves

Kohlhoff

et al. 2022

Virol J

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“…The ZIKV genome is a single-stranded, positive-sense RNA molecule, approximately 11,000 nucleotides in length, with two untranslated regions and one open reading frame. The genome is translated and processed into ten proteins–three structural proteins [envelope (E), membrane (M), nucleocapsid), and seven nonstructural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5] [ 17 ] ( Figure 1 ). Among the three structural proteins, the capsid protein is responsible for encapsulating the viral genomic RNA to form the nucleocapsid of ZIKV.…”

Section: Zikv Biologymentioning

confidence: 99%

Rational Development of Live-Attenuated Zika Virus Vaccines

Adam

Lee²

2023

Pathogens

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Zika virus (ZIKV), a re-emerging mosquito-borne flavivirus, has caused outbreaks in Africa, Asia, the Pacific, and, more recently, in the Americas. ZIKV has been associated with the neurological autoimmune disorder Guillain–Barre syndrome in adults and congenital Zika syndrome in fetuses and infants, including microcephaly, spontaneous abortion, and intrauterine growth restriction. It is considered to be a major threat to global public health due to its unprecedented clinical impact on humans. Currently, there are no specific prophylactics or therapeutics available to prevent or treat ZIKV infection. The development of a safe and efficacious ZIKV vaccine remains a global health priority. Since the recent outbreak, multiple platforms have been used in the development of candidate ZIKV vaccines. The candidate vaccines have been shown to elicit strong T cell and neutralization antibody responses and protect against ZIKV infection in animal models. Some candidates have progressed successfully to clinical trials. Live-attenuated vaccines, which induce rapid and durable protective immunity, are one of the most important strategies for controlling flavivirus diseases. In this review, we discuss recent progress in the development of candidate live-attenuated ZIKV vaccines.

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“…Mutations arising in the ZIKV Asian/American lineage have been shown to assist the virus in its acquisition by vectors as well as adaptation to hosts. The NS1 of many flaviviruses, including DENV and ZIKV, is secreted by host cells and is present in host blood in large quantities during acute infection [73][74][75][76]. In addition to assisting in the pathogenesis of flaviviruses in the host, when acquired with virions, NS1 enhances viral infectivity in mosquitoes by overcoming the mosquito midgut immune barrier [74].…”

Section: Zika Virusmentioning

confidence: 99%

Adaptive Evolution as a Driving Force of the Emergence and Re-Emergence of Mosquito-Borne Viral Diseases

Cheng

2022

Viruses

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Emerging and re-emerging mosquito-borne viral diseases impose a significant burden on global public health. The most common mosquito-borne viruses causing recent epidemics include flaviviruses in the family Flaviviridae, including Dengue virus (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV) and West Nile virus (WNV) and Togaviridae viruses, such as chikungunya virus (CHIKV). Several factors may have contributed to the recent re-emergence and spread of mosquito-borne viral diseases. Among these important causes are the evolution of mosquito-borne viruses and the genetic mutations that make them more adaptive and virulent, leading to widespread epidemics. RNA viruses tend to acquire genetic diversity due to error-prone RNA-dependent RNA polymerases, thus promoting high mutation rates that support adaptation to environmental changes or host immunity. In this review, we discuss recent findings on the adaptive evolution of mosquito-borne viruses and their impact on viral infectivity, pathogenicity, vector fitness, transmissibility, epidemic potential and disease emergence.

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ZIKV viral proteins and their roles in virus-host interactions

Cited by 11 publications

References 100 publications

Searching for plant-derived antivirals against dengue virus and Zika virus

Searching for plant-derived antivirals against dengue virus and Zika virus

Rational Development of Live-Attenuated Zika Virus Vaccines

Adaptive Evolution as a Driving Force of the Emergence and Re-Emergence of Mosquito-Borne Viral Diseases

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