Peptide-Based Membrane Fusion Inhibitors Targeting HCoV-229E Spike Protein HR1 and HR2 Domains

Xia, Shuai; Xu, Wei; Wang, Qian; Wang, Cong; Chen, Hua; Li, Weihua; Lu, Lu; Jiang, Shibo

doi:10.3390/ijms19020487

Cited by 64 publications

(61 citation statements)

References 53 publications

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“…They exhibit broad-spectrum activities against numerous enveloped viruses and may be active against CoVs [164][165][166][167]. In addition to the above-mentioned molecules, there are numerous peptide-based inhibitors of coronaviruses [168].…”

Section: Figure 13mentioning

confidence: 99%

Recent discovery and development of inhibitors targeting coronaviruses

Pillaiyar

Meenakshisundaram²,

Manickam

2020

Drug Discovery Today

329

323

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Section: Figure 13mentioning

confidence: 99%

Recent discovery and development of inhibitors targeting coronaviruses

Pillaiyar

Meenakshisundaram²,

Manickam

2020

Drug Discovery Today

329

323

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“…Besides, in vivo assays showed that 229E-HR2P could retain its antiviral activity in both upper and lower respiratory tracts when administered intranasally. In the end, the authors suggested that 229E-HR2P could become an antiviral drug to be used along with different antiviral molecules with a different mechanism of action, possibly exerting synergistic activity [168].…”

Section: Avps Against Coronavirusmentioning

confidence: 99%

Antiviral peptides as promising therapeutic drugs

Boas

Campos

Berlanda

et al. 2019

Cell. Mol. Life Sci.

254

175

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While scientific advances have led to large-scale production and widespread distribution of vaccines and antiviral drugs, viruses still remain a major cause of human diseases today. The ever-increasing reports of viral resistance and the emergence and re-emergence of viral epidemics pressure the health and scientific community to constantly find novel molecules with antiviral potential. This search involves numerous different approaches, and the use of antimicrobial peptides has presented itself as an interesting alternative. Even though the number of antimicrobial peptides with antiviral activity is still low, they already show immense potential to become pharmaceutically available antiviral drugs. Such peptides can originate from natural sources, such as those isolated from mammals and from animal venoms, or from artificial sources, when bioinformatics tools are used. This review aims to shed some light on antimicrobial peptides with antiviral activities against human viruses and update the data about the already well-known peptides that are still undergoing studies, emphasizing the most promising ones that may become medicines for clinical use.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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“…Briefly, 100 PFU of ZIKV was incubated with 2-fold serial dilutions of mouse sera at 37 • C for 1.5 h, which were added to Vero E6 cells and incubated at 37 • C for 1 h. The cells were then overlaid with DMEM containing 1% carboxymethyl cellulose and 2% FBS, cultured at 37 • C for 4-5 days and further stained with 0.5% crystal violet. The neutralizing titer based on the serum neutralizations at a 50% plaque reduction (PRNT 50 ) was calculated using the CalcuSyn computer program [27,33,34].…”

Section: Zikv Plaque-forming Assay and Plaque Reduction Neutralizatiomentioning

confidence: 99%

Effects of Adjuvants on the Immunogenicity and Efficacy of a Zika Virus Envelope Domain III Subunit Vaccine

et al. 2019

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Zika virus (ZIKV), a mosquito-borne flavivirus, has attracted global attention due to its close association with congenital Zika syndrome and neurological diseases, and transmission through additional routes, such as sexual contact. Currently there are no vaccines approved for ZIKV, and thus, there is an urgent need to develop an effective and safe ZIKV vaccine. Domain III (DIII) of the ZIKV envelope (E) protein is an important vaccine target, and a vaccine developed using a mutant DIII of E (EDIII) protein protects adult and pregnant mice, and unborn offspring, against ZIKV infection. Here, we have used immunocompetent BALB/c mice treated with anti-interferon-α/β receptor 1 (Ifnar1) antibodies to investigate whether three adjuvants (aluminum (Alum), monophosphoryl lipid A (MPL), and MF59), either alone or in combination, could improve the efficacy of this EDIII subunit vaccine. Our data show that, although vaccine formulated with a single adjuvant induced a specific antibody and cellular immune response, and reduced viral load in mice challenged with ZIKV, the combination of Alum and MPL adjuvants led to a more robust and balanced immune response, stronger neutralizing activity against three recent ZIKV human strains, and greater protection against a high-dose ZIKV challenge. Particularly, the combination of Alum with MPL significantly reduced viral titers and viral RNA copy numbers in sera and tissues, including the male reproductive organs. Overall, this study has identified the combination of Alum and MPL as the most effective adjuvant for ZIKV EDIII subunit vaccines, and it has important implications for subunit vaccines against other enveloped viruses, including non-ZIKV flaviviruses.Vaccines 2019, 7, 161 2 of 16 with microcephaly, fetal demise, and other congenital disorders [4][5][6]. Thus, ZIKV has emerged as a global health threat and there is an urgent requirement for an effective vaccine to combat ZIKV-associated diseases.The ZIKV genome encodes a single polyprotein, which is processed into three structural proteins (capsid (C), precursor of membrane/membrane (prM/M), and envelope (E)) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) [7][8][9]. The E protein has important roles in infection and pathogenesis, is involved in virus binding to target cells and membrane fusion, and also serves as an important vaccine target [7,8]. The E protein is a transmembrane protein and consists of three domains termed I, II, and III (DI-DIII), a fusion loop (FL), and a stalk region (S) [8]. The DI-DII region of ZIKV E protein is a target for cross-reactive antibodies with other flaviviruses, such as dengue virus (DENV) and West Nile virus (WNV), whereas the DIII domain induces ZIKV-specific antibodies [10][11][12], and therefore, is a key target for ZIKV vaccine development. ZIKV vaccine candidates under development include inactivated virus, live attenuated virus, DNA, mRNA, viral vectors, virus-like particles (VLPs), and viral proteins (or subunit vaccines) [13][14][15][16]. Although ma...

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Peptide-Based Membrane Fusion Inhibitors Targeting HCoV-229E Spike Protein HR1 and HR2 Domains

Cited by 64 publications

References 53 publications

Recent discovery and development of inhibitors targeting coronaviruses

Recent discovery and development of inhibitors targeting coronaviruses

Antiviral peptides as promising therapeutic drugs

Effects of Adjuvants on the Immunogenicity and Efficacy of a Zika Virus Envelope Domain III Subunit Vaccine

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