Fusion-inhibition peptide broadly inhibits influenza virus and SARS-CoV-2, including Delta and Omicron variants

Zhao, Hanjun; Meng, Xinjie; Zheng, Peng; Lam, Hoiyan; Zhang, Chuyuan; Zhou, Xinxin; Chan, Jasper Fuk‐Woo; Kao, Richard Yi Tsun; To, Kelvin Kai-Wang; Yuen, Kwok‐Yung

doi:10.1080/22221751.2022.2051753

Cited by 20 publications

(16 citation statements)

References 48 publications

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“…Viruses used in this study included A/Hong Kong/415742Md/2009 (H1N1), 44 A/Netherlands/219/2003 (H7N7), 45 and SARS-CoV-2 variants. 46 – 48 Influenza A viruses were cultured in MDCK cells, while SARS-CoV-2 variants were cultured in VeroE6 or VeroE6-TMPRSS2 cells,…”

Section: Methodsmentioning

confidence: 99%

Peptidic defective interfering gene nanoparticles against Omicron, Delta SARS-CoV-2 variants and influenza A virus in vivo

Zhao

Zhang

Lam

et al. 2022

Sig Transduct Target Ther

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Defective interfering genes (DIGs) are short viral genomes and interfere with wild-type viral replication. Here, we demonstrate that the new designed SARS-CoV-2 DIG (CD3600) can significantly inhibit the replication of SARS-CoV-2 including Alpha, Delta, Kappa and Omicron variants in human HK-2 cells and influenza DIG (PAD4) can significantly inhibit influenza virus replication in human A549 cells. One dose of influenza DIGs prophylactically protects 90% mice from lethal challenge of A(H1N1)pdm09 virus and CD3600 inhibits SARS-CoV-2 replication in hamster lungs when DIGs are administrated to lungs one day before viral challenge. To further investigate the gene delivery vector in the respiratory tract, a peptidic TAT2-P1&LAH4, which can package genes to form small spherical nanoparticles with high endosomal escape ability, is demonstrated to dramatically increase gene expression in the lung airway. TAT2-P1&LAH4, with the dual-functional TAT2-P1 (gene-delivery and antiviral), can deliver CD3600 to significantly inhibit the replication of Delta and Omicron SARS-CoV-2 in hamster lungs. This peptide-based nanoparticle system can effectively transfect genes in lungs and deliver DIGs to inhibit SARS-CoV-2 variants and influenza virus in vivo, which provides the new insight into the drug delivery system for gene therapy against respiratory viruses.

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Section: Methodsmentioning

confidence: 99%

Peptidic defective interfering gene nanoparticles against Omicron, Delta SARS-CoV-2 variants and influenza A virus in vivo

Zhao

Zhang

Lam

et al. 2022

Sig Transduct Target Ther

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“…The low pH-dependent HA-mediated fusion can take place mainly in the endosomes. No syncytia formation takes place when no artificial challenge is introduced by treating the cells with the low pH [33]. However, SARS-CoV-2 spike-ACE2 binding can induce the syncytia in the normal condition of the cell culture without additional artificial treatment, such as the low pH challenge.…”

Section: The Comparison Of Cell Fusions Mediated By the Influenza Vir...mentioning

confidence: 99%

“…Class I fusion proteins can form a coiled-coil six-helix bundle (6HB) structure in the post-fusion state, which is considered as a conserved antiviral target. Using this strategy, studies are able to design relatively broad-spectrum antiviral lipopeptides against both the influenza virus and the coronavirus [65], specifically for the influenza virus by targeting the HA stalk region [33], and specifically for the coronavirus including SARS-CoV-2 by targeting the heptad repeat 1 (HR1) region of the spike protein [66].…”

Section: Preventing Conformation Changesmentioning

confidence: 99%

Comparison of Cell Fusions Induced by Influenza Virus and SARS-CoV-2

Zhang

Meng

Zhao

2022

IJMS

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Virus–cell fusion is the key step for viral infection in host cells. Studies on virus binding and fusion with host cells are important for understanding the virus–host interaction and viral pathogenesis for the discovery of antiviral drugs. In this review, we focus on the virus–cell fusions induced by the two major pandemic viruses, including the influenza virus and SARS-CoV-2. We further compare the cell fusions induced by the influenza virus and SARS-CoV-2, especially the pH-dependent fusion of the influenza virus and the fusion of SARS-CoV-2 in the type-II transmembrane serine protease 2 negative (TMPRSS2-) cells with syncytia formation. Finally, we present the development of drugs used against SARA-CoV-2 and the influenza virus through the discovery of anti-fusion drugs and the prevention of pandemic respiratory viruses.

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“… 1 Notably, replication of the Omicron variant appears to be confined to the upper airway tract, a finding that correlates with less severe disease. 2 , 3 …”

Section: Introductionmentioning

confidence: 99%

“…1 Notably, replication of the Omicron variant appears to be confined to the upper airway tract, a finding that correlates with less severe disease. 2,3 Removal and neutralization of potentially harmful substances from inhaled air are main functions of the airway epithelium, which consists of multiple cell types. 1) Basal cells are the progenitor cells that differentiate into the epithelial cell types.…”

Section: Introductionmentioning

confidence: 99%

NF-κB inhibitor alpha has a cross-variant role during SARS-CoV-2 infection in ACE2-overexpressing human airway organoids

Simoneau¹,

Chen²,

Xing³

et al. 2022

Preprint

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As SARS-CoV-2 continues to spread worldwide, simple and tractable primary airway cell models that accurately recapitulate the cell-intrinsic response to arising viral variants are needed. Here we describe an adult stem cell-derived human airway organoid model overexpressing the ACE2 receptor that supports robust viral replication while maintaining 3D architecture and cellular diversity of the airway epithelium. ACE2-OE organoids were infected with SARS-CoV-2 variants and subjected to single-cell RNA-sequencing. NF-kB inhibitor alpha was consistently upregulated in infected epithelial cells, and its mRNA expression positively correlated with infection levels. Single-cell imaging showed more IkBa expression in infected cells than uninfected bystander cells, but found concurrent nuclear translocation of NF-kB that IkBa usually prevents. Overexpressing a non-degradable IkBa mutant reduced NF-kB translocation and increased viral infection. These data identify IkBa as a cellular rheostat that controls viral replication by tuning NF-kB. Incomplete NF-kB control in infected cells may promote inflammation and severe disease.

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Fusion-inhibition peptide broadly inhibits influenza virus and SARS-CoV-2, including Delta and Omicron variants

Cited by 20 publications

References 48 publications

Peptidic defective interfering gene nanoparticles against Omicron, Delta SARS-CoV-2 variants and influenza A virus in vivo

Peptidic defective interfering gene nanoparticles against Omicron, Delta SARS-CoV-2 variants and influenza A virus in vivo

Comparison of Cell Fusions Induced by Influenza Virus and SARS-CoV-2

NF-κB inhibitor alpha has a cross-variant role during SARS-CoV-2 infection in ACE2-overexpressing human airway organoids

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