Structures and Functions of the Envelope Glycoprotein in Flavivirus Infections

Zhang, Xingcui; Jia, Renyong; Shen, Haoyue; Wang, Mingshu; Yin, Zhongqiong; Cheng, Anchun

doi:10.3390/v9110338

Cited by 138 publications

(122 citation statements)

References 107 publications

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“…The C protein is important for encapsidation that protects the DENV genome [10]. The prM maintains the spatial structure of the E protein [11]. The E protein has been implicated in the membrane fusion between host cells and DENV particles [11].…”

Section: Denv Genome and Encoded Proteinsmentioning

confidence: 99%

Structure-Based Design of Antivirals against Envelope Glycoprotein of Dengue Virus

Anasir

Ramanathan

Poh

2020

Viruses

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Dengue virus (DENV) presents a significant threat to global public health with more than 500,000 hospitalizations and 25,000 deaths annually. Currently, there is no clinically approved antiviral drug to treat DENV infection. The envelope (E) glycoprotein of DENV is a promising target for drug discovery as the E protein is important for viral attachment and fusion. Understanding the structure and function of DENV E protein has led to the exploration of structure-based drug discovery of antiviral compounds and peptides against DENV infections. This review summarizes the structural information of the DENV E protein with regards to DENV attachment and fusion. The information enables the development of antiviral agents through structure-based approaches. In addition, this review compares the potency of antivirals targeting the E protein with the antivirals targeting DENV multifunctional enzymes, repurposed drugs and clinically approved antiviral drugs. None of the current DENV antiviral candidates possess potency similar to the approved antiviral drugs which indicates that more efforts and resources must be invested before an effective DENV drug materializes.

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Section: Denv Genome and Encoded Proteinsmentioning

confidence: 99%

Structure-Based Design of Antivirals against Envelope Glycoprotein of Dengue Virus

Anasir

Ramanathan

Poh

2020

Viruses

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“…The main antigenic determinant of the virus is the envelope glycoprotein (E), since it is displayed on the surface of the mature virus particle and can be targeted by a number of neutralizing antibodies [9,10]. Neutralizing antibodies generated by approved vaccines for yellow fever virus, Japanese encephalitis virus, and tick-borne encephalitis virus, which are closely related to ZIKV, appear to have a correlation with viral protection [11,12].…”

Section: Introductionmentioning

confidence: 99%

Codelivery of improved immune complex and virus-like particle vaccines containing Zika virus envelope domain III synergistically enhances immunogenicity

Diamos

Pardhe

Sun

et al. 2020

Vaccine

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a b s t r a c tZika virus (ZIKV) reemergence poses a significant health threat especially due to its risks to fetal development, necessitating safe and effective vaccines that can protect pregnant women. Zika envelope domain III (ZE3) has been identified as a safe and effective vaccine candidate, however it is poorly immunogenic. We previously showed that plant-made recombinant immune complex (RIC) vaccines are a robust platform to improve the immunogenicity of weak antigens. In this study, we altered the antigen fusion site on the RIC platform to accommodate N-terminal fusion to the IgG heavy chain (N-RIC), and thus a wider range of antigens, with a resulting 40% improvement in RIC expression over the normal C-terminal fusion (C-RIC). Both types of RICs containing ZE3 were efficiently assembled in plants and purified to >95% homogeneity with a simple one-step purification. Both ZE3 RICs strongly bound complement receptor C1q and elicited strong ZE3-specific antibody titers that correlated with ZIKV neutralization. When either N-RIC or C-RIC was codelivered with plant-produced hepatitis B core (HBc) virus-like particles (VLP) displaying ZE3, the combination elicited 5-fold greater antibody titers (>1,000,000) and more strongly neutralized ZIKV than either RICs or VLPs alone, after only two doses without adjuvant. These findings demonstrate that antigens that require a free N-terminus for optimal antigen display can now be used with the RIC system, and that plant-made RICs and VLPs are highly effective vaccines targeting ZE3. Thus, the RIC platform can be more generally applied to a wider variety of antigens.

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“…The genome contains only one open reading frame (ORF) flanked by 5' and 3'untranslated regions (UTRs) that encodes a polyprotein. The translated polyprotein is directed into host endoplasmic reticulum (ER) membrane by signal sequences and cleaved by host protease into three structural proteins, a nucleocapsid protein (C protein), a precursor membrane glycoprotein (prM protein) and a glycosylated envelope protein (E protein), as well as seven non-structural (NS) proteins [15][16][17][18][19]. The C protein is responsible for encapsulation of the virus to protect the genetic material.…”

Section: Introductionmentioning

confidence: 99%

Computational Prediction of Multi-Epitopes Vaccine from Envelope E Protein against Louping Ill Virus via Reverse Vaccinology

2020

JCEI

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Louping ill disease is a zoonotic viral disease caused by louping ill virus in the genus Flavivirus. It belongs to the tick-borne flavivirus that is a part of the tick-borne encephalitis virus complex.The envelope E protein of louping ill virus is the major structural protein that plays an important role in membrane binding and inducing a protective immune response.The aim of the present study was to design multi epitopes vaccine from the envelope E glycoprotein against louping ill virus using immunoinformatic tools that elicited humoral and cellular immunity. Eighteen envelope E protein sequences were retrieved from NCBI and subjected to various immunoinformatics tools from IEDB to assess their conservancy, surface accessibility and antigenicity as promising epitopes against B cells. The binding affinity of the conserved predicted epitopes was analyzed against MHC-I and MHC-II alleles of the T cells. The predicted epitopes were further assessed for their population coverage. For B-cell 25, 18 and 12 epitopes were predicted as linear conserved epitopes, surface accessibility and antigenic respectively. However, nine epitopes overlapped all the B cell prediction tools. Among them three epitopes (205-TAEHLP-210,336-KPCR-339 and 349-SPDV-352) were proposed as B cell epitopes. For T cell, 75 epitopes were found to interact with MHC-I alleles. The epitopes 130-YVYDANKV-138and356-MLITPNPTI-364 were proposed as a peptide vaccine since they interacted with the highest number of MHC-1 alleles.Moreover a total of 195core epitopes were found to interact with MHC-II alleles. The core epitopes 130-YVYDANKV-138, 219-WFNDLALPW-227, 415-VIGEHAWDF-423 and 462-VALAWLGLN-470 interacted with higher number of MHC-II alleles and proposed as vaccine since they demonstrated high affinity to MHC-II alleles.The population coverage epitopes set for MHC-I and MHC-II alleles was 74.69% and 99.98%, respectively. While the epitopes set for all T cell, proposed epitopes was 100%. Nine epitopes were predicted eliciting B and T cells and proposed as vaccine candidates against louping ill virus. However, these proposed epitopes require clinical trials studies to ensure their efficacy as vaccine candidates.

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Structures and Functions of the Envelope Glycoprotein in Flavivirus Infections

Cited by 138 publications

References 107 publications

Structure-Based Design of Antivirals against Envelope Glycoprotein of Dengue Virus

Structure-Based Design of Antivirals against Envelope Glycoprotein of Dengue Virus

Codelivery of improved immune complex and virus-like particle vaccines containing Zika virus envelope domain III synergistically enhances immunogenicity

Computational Prediction of Multi-Epitopes Vaccine from Envelope E Protein against Louping Ill Virus via Reverse Vaccinology

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