An Antiviral Peptide from Alopecosa nagpag Spider Targets NS2B–NS3 Protease of Flaviviruses

Ji, Mengyao; Zhu, Tengyu; Xing, Meichen; Luan, Ning; Mwangi, James; Yan, Xiuwen; Mo, Guoxiang; Rong, Mingqiang; Li, Bowen; Lai, Ren; Jin, Lin

doi:10.3390/toxins11100584

Cited by 25 publications

(22 citation statements)

References 37 publications

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“…Cyclic peptides that mimic the substrates of the DENV NS2B-NS3 protein exhibited inhibitory activities on viral protease and anti-viral activities against DENV-2 60 . Cationic peptides from natural sources, such as plectasin, which is a fungus-derived defensin, as well as latarcin-1 and defensin-like An1a peptides from spider venom targeted NS2B-NS3 protease of DENV-2, resulting in the inhibition of viral protease activity and DENV-2 replication 61 – 63 . Di- and tripeptides with β-lactam moiety could serve as electrophilic warheads in the reduction of DENV NS2B-NS3 protease activity and infectious virus production 64 .…”

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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“…Currently, no effective vaccines or antiviral drugs have been approved for ZIKV. Venom systems have been used for predation and defense and venom-derived peptides have become an important source of antivirals (Cecilio et al, 2013;Hong et al, 2014;Holthausen et al, 2017;Ji et al, 2019). For example, a representative defensin-like antiviral peptide BmKDfsin4 from the scorpion Mesobuthus martensii Karsch was reported to inhibit Hepatitis B virus replication (Zeng et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Snake Cathelicidin Derived Peptide Inhibits Zika Virus Infection

Xing

Jie

et al. 2020

Front. Microbiol.

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Zika virus (ZIKV) is a mosquito-borne virus belonging to the genus Flavivirus and has reemerged in recent years with epidemic potential. ZIKV infection may result in severe syndromes such as neurological complications and microcephaly in newborns. Therefore, ZIKV has become a global public health threat and currently there is no approved specific drug for its treatment. Animal venoms are important resources of novel drugs. Cathelicidin-BF (BF-30) is a defensive peptide identified from Bungarus fasciatus snake venom and has been shown to be an excellent template for applicable peptide design. In this study, we found that ZY13, one of the peptidic analogs of BF-30, inhibits ZIKV infection in vitro and in vivo. Mechanistic studies revealed that ZY13 can directly inactivate ZIKV and reduce the production of infectious virions. Further studies also indicated that administration of ZY13 strengthen the host antiviral immunity via AXL-SOCS (suppressor of cytokine signaling protein) pathway. Additionally, the results of mouse experiment suggest that ZY13 efficiently restrict ZIKV infection and improve the growth defects of ZIKV-infected mouse pups. Together, our findings not only demonstrate that ZY13 might be a candidate for anti-ZIKV drug, but also indicated the importance of animal venom peptides as templates for antivirals development.

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“…In addition, spider venom peptides are able to exert antiviral effects. Av-LCTX-An1a is a defense peptide from the venom of the Alopecosa nagpag spider that presents antiviral activities against flavivirus infection by acting as an inhibitor of the viral protease NS2B-NS3 [29]. The presence of these antimicrobials has driven scientists to use them as templates for the production of novel antibiotics.…”

Section: Antimicrobial Agents From Spidersmentioning

confidence: 99%

Antimicrobials from Venomous Animals: An Overview

et al. 2020

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The inappropriate or excessive use of antimicrobial agents caused an emerging public health problem due to the resulting resistance developed by microbes. Therefore, there is an urgent need to develop effective antimicrobial strategies relying on natural agents with different mechanisms of action. Nature has been known to offer many bioactive compounds, in the form of animal venoms, algae, and plant extracts that were used for decades in traditional medicine. Animal venoms and secretions have been deeply studied for their wealth in pharmaceutically promising molecules. As such, they were reported to exhibit many biological activities of interest, such as antibacterial, antiviral, anticancer, and anti-inflammatory activities. In this review, we summarize recent findings on the antimicrobial activities of crude animal venoms/secretions, and describe the peptides that are responsible of these activities.

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An Antiviral Peptide from Alopecosa nagpag Spider Targets NS2B–NS3 Protease of Flaviviruses

Cited by 25 publications

References 37 publications

Peptides targeting dengue viral nonstructural protein 1 inhibit dengue virus production

Peptides targeting dengue viral nonstructural protein 1 inhibit dengue virus production

Snake Cathelicidin Derived Peptide Inhibits Zika Virus Infection

Antimicrobials from Venomous Animals: An Overview

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