Model-Guided Engineering of NS1-Truncated Influenza OP7 Particles with Enhanced Interferon-Mediated Antiviral Activity
- 1Max Planck Institute for Dynamics of Complex Technical Systems, Bioprocess Engineering, Magdeburg, Germany
Abstract
Defective interfering particles (DIPs) represent promising antivirals against influenza A virus (IAV), yet strategies to further enhance their antiviral activity remain largely unexplored. Here, we engineered a next-generation OP7 DIP by truncating the viral interferon (IFN) antagonist non-structural protein 1 (NS1) to enhance IFN-mediated antiviral activity. A previously validated mathematical multiscale model predicted that loss of NS1 function would enhance antiviral activity, providing a mechanistic rationale for this design. We engineered OP7-trNS1 DIP, established a cell culture-based production process yielding infectious virus-free material, and evaluated its antiviral activity in human lung epithelial cells in vitro. OP7-trNS1 inhibited IAV replication by approx. two orders of magnitude more effectively than the parental OP7 DIP while inducing a stronger IFN response, consistent with the model predictions. Together, these findings demonstrate that reducing viral IFN antagonism is a viable strategy for rationally enhancing DIP antiviral activity and establish OP7-trNS1 as a promising candidate for further preclinical development.
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BibTeX
@misc{piasecka2026modelguided,
title = {{Model-Guided Engineering of NS1-Truncated Influenza OP7 Particles with Enhanced Interferon-Mediated Antiviral Activity}},
author = {J. Piasecka and D. Ruediger and U. Reichl and S. Y. Kupke},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.18.752587},
url = {https://www.biorxiv.org/content/10.64898/2026.09.18.752587v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Model-Guided Engineering of NS1-Truncated Influenza OP7 Particles with Enhanced Interferon-Mediated Antiviral Activity
AU - J. Piasecka
AU - D. Ruediger
AU - U. Reichl
AU - S. Y. Kupke
PY - 2026
DA - 2026/09/18
PB - bioRxiv
DO - 10.64898/2026.09.18.752587
UR - https://www.biorxiv.org/content/10.64898/2026.09.18.752587v1
AB - Defective interfering particles (DIPs) represent promising antivirals against influenza A virus (IAV), yet strategies to further enhance their antiviral activity remain largely unexplored. Here, we engineered a next-generation OP7 DIP by truncating the viral interferon (IFN) antagonist non-structural protein 1 (NS1) to enhance IFN-mediated antiviral activity. A previously validated mathematical multiscale model predicted that loss of NS1 function would enhance antiviral activity, providing a mechanistic rationale for this design. We engineered OP7-trNS1 DIP, established a cell culture-based production process yielding infectious virus-free material, and evaluated its antiviral activity in human lung epithelial cells in vitro. OP7-trNS1 inhibited IAV replication by approx. two orders of magnitude more effectively than the parental OP7 DIP while inducing a stronger IFN response, consistent with the model predictions. Together, these findings demonstrate that reducing viral IFN antagonism is a viable strategy for rationally enhancing DIP antiviral activity and establish OP7-trNS1 as a promising candidate for further preclinical development.
ER -