Antiviral activity of phage display-selected peptides against Japanese encephalitis virus infection in vitro and in vivo

Wei, Jianchao; Hameed, Muddassar; Wang, Xin; Zhang, Junjie; Guo, Shuang; Anwar, Muhammad Naveed; Pang, Linlin; Liu, Ke; Li, Beibei; Shao, Donghua; Qiu, Yafeng; Zhong, Dexing; Zhou, Bin; Ma, Zhiyong

doi:10.1016/j.antiviral.2019.104673

Cited by 28 publications

(28 citation statements)

References 67 publications

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“…In this study, we proposed DENV NS1 as a novel target for inhibition of DENV infection by identifying specific peptide inhibitors from a Ph.D.-12 phage display peptide library. Utilization of the same peptide library proved successful for identifying a set of peptides binding to purified DENV-2 and E protein (amino acid residues 1–400 and domain III) of Japanese encephalitis virus (JEV), a related flavivirus, and to demonstrate peptide inhibition of DENV-2 infection in Vero cells and JEV infection in BHK-21 cells during the step of virus entry as well as in a mouse model with lethal JEV challenge 67 – 69 . Our results of biopanning assays revealed that the specificity of DENV NS1 binding by phage clones increased over time as evidenced by the efficiency of phage recovery after each round of selection, and that 36 out of 80 phage clones from the third round of biopanning satisfied our selection criteria based on DENV NS1 binding activities and displayed 11 different sequences of 12-mer peptides.…”

Section: Discussionmentioning

confidence: 99%

Peptides targeting dengue viral nonstructural protein 1 inhibit dengue virus production

Songprakhon

Thaingtamtanha

Limjindaporn

et al. 2020

Sci Rep

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Viruses manipulate the life cycle in host cells via the use of viral properties and host machineries. Development of antiviral peptides against dengue virus (DENV) infection has previously been concentrated on blocking the actions of viral structural proteins and enzymes in virus entry and viral RNA processing in host cells. In this study, we proposed DENV NS1, which is a multifunctional nonstructural protein indispensable for virus production, as a new target for inhibition of DENV infection by specific peptides. We performed biopanning assays using a phage-displayed peptide library and identified 11 different sequences of 12-mer peptides binding to DENV NS1. In silico analyses of peptide-protein interactions revealed 4 peptides most likely to bind to DENV NS1 at specific positions and their association was analysed by surface plasmon resonance. Treatment of Huh7 cells with these 4 peptides conjugated with N-terminal fluorescent tag and C-terminal cell penetrating tag at varying time-of-addition post-DENV infection could inhibit the production of DENV-2 in a time-and dosedependent manner. The inhibitory effects of the peptides were also observed in other virus serotypes (DENV-1 and DENV-4), but not in DENV-3. These findings indicate the potential application of peptides targeting DENV NS1 as antiviral agents against DENV infection. Dengue virus (DENV) infection is a major and increasing public health problem worldwide. There are approximately 390 million infections, 500,000 severe cases with hospitalization, and a 2.5% mortality rate each year 1,2. Although the majority of individuals experiencing DENV infection are asymptomatic, approximately one-fourth of the infected cases develop a wide range of clinical manifestations of dengue disease with unclear pathogenic mechanisms 3,4. To date, there is no specific anti-viral drug available for the treatment of DENV infection. A licensed dengue vaccine also has some limitations for use in naïve individuals not previously infected by DENV and in children less than 9 years of age 5,6. Consequently, the development of an alternative strategy to combat DENV infection and severe dengue is still needed. DENV is a positive, single-stranded, enveloped RNA virus belonging to the family Flaviviridae, and it has 4 distinct serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) 7. Infection with any DENV serotype can generate

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Section: Discussionmentioning

confidence: 99%

Peptides targeting dengue viral nonstructural protein 1 inhibit dengue virus production

Songprakhon

Thaingtamtanha

Limjindaporn

et al. 2020

Sci Rep

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“…Although it is common to screen in-house phage display libraries, the commercial peptide libraries (e.g., New England BioLabs (NEB) and MoBiTec GmbH) have also been used to develop peptide-based antivirals [50][51][52]. For instance, 7-mer and 12-mer linear peptide libraries of NEB have been widely used to identify antivirals for various viruses (e.g., avian infectious bronchitis virus (IBV), dengue virus serotype 2 (DENV-2), Macrobrachium rosenbergii nodavirus (MrNv), Japanese encephalitis virus (JEV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis (TGE) virus, infectious salmon anemia virus (ISAV), bovine ephemeral fever virus (BEFV), influenza B virus, and Mink enteritis virus (MEV)) (Table 1) [53][54][55][56][57][58][59][60][61][62][63][64]. Cao et al [65] employed a 12-mer phage display peptide library to develop antivirals against PEDV, the causative agent of persistent diarrhea in swine.…”

Section: Peptide Librariesmentioning

confidence: 99%

Discovery of Antivirals Using Phage Display

Sokullu

Gauthier

Coulombe

2021

Viruses

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The latest coronavirus disease outbreak, COVID-19, has brought attention to viral infections which have posed serious health threats to humankind throughout history. The rapid global spread of COVID-19 is attributed to the increased human mobility of today’s world, yet the threat of viral infections to global public health is expected to increase continuously in part due to increasing human–animal interface. Development of antiviral agents is crucial to combat both existing and novel viral infections. Recently, there is a growing interest in peptide/protein-based drug molecules. Antibodies are becoming especially predominant in the drug market. Indeed, in a remarkably short period, four antibody therapeutics were authorized for emergency use in COVID-19 treatment in the US, Russia, and India as of November 2020. Phage display has been one of the most widely used screening methods for peptide/antibody drug discovery. Several phage display-derived biologics are already in the market, and the expiration of intellectual property rights of phage-display antibody discovery platforms suggests an increment in antibody drugs in the near future. This review summarizes the most common phage display libraries used in antiviral discovery, highlights the approaches employed to enhance the antiviral potency of selected peptides/antibody fragments, and finally provides a discussion about the present status of the developed antivirals in clinic.

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“…Subsequently, 10 mice/group were challenged via an intraperitoneal route with 5 × 10 6 PFU of lethal JEV N28 strain 28 days after the first immunization, and the survival curves of mice were constructed for the 20 days continuously following challenge. Blood samples from 5 mice/group were taken from the central tail vein 2 and 3 days after challenge to detect viremia levels through qRT-PCR [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

“…The remaining guinea pigs were challenged with a lethal dose of 5 × 10 6 PFU of PPV Nanjing 200,801 on the 42nd day and monitored for a further 14 days. After this, guinea pigs were sacrificed and the contents of PPV in the spleen were measured through real-time PCR (RT-PCR) [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

A Novel Recombinant Virus-Like Particles Displaying B and T Cell Epitopes of Japanese Encephalitis Virus Offers Protective Immunity in Mice and Guinea Pigs

Anwar

Jiang

et al. 2021

Vaccines

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Virus-like particles (VLPs) are non-replicative vectors for the delivery of heterologous epitopes and are considered one of the most potent inducers of cellular and humoral immune responses in mice and guinea pigs. In the present study, VLP-JEVe was constructed by the insertion of six Japanese encephalitis virus (JEV) envelope protein epitopes into different surface loop regions of PPV VP2 by the substitution of specific amino acid sequences without altering the assembly of the virus; subsequently, the protective efficacy of this VLP-JEVe was evaluated against JEV challenge in mice and guinea pigs. Mice immunized with the VLP-JEVe antigen developed high titers of neutralizing antibodies and 100% protection against lethal JEV challenge. The neutralizing and hemagglutination inhibition (HI) antibody responses were also induced in guinea pigs vaccinated with VLP-JEVe. In addition, immunization with VLP-JEVe in mice induced effective neutralizing antibodies and protective immunity against PPV (porcine parvovirus) challenge in guinea pigs. These studies suggest that VLP-JEVe produced as described here could be a potential candidate for vaccine development.

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Antiviral activity of phage display-selected peptides against Japanese encephalitis virus infection in vitro and in vivo

Cited by 28 publications

References 67 publications

Peptides targeting dengue viral nonstructural protein 1 inhibit dengue virus production

Peptides targeting dengue viral nonstructural protein 1 inhibit dengue virus production

Discovery of Antivirals Using Phage Display

A Novel Recombinant Virus-Like Particles Displaying B and T Cell Epitopes of Japanese Encephalitis Virus Offers Protective Immunity in Mice and Guinea Pigs

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