Virus-host interaction networks as new antiviral drug targets for IAV and SARS-CoV-2

ABSTRACT

Currently, SARS-CoV-2, especially the Omicron strain, is ravaging the world and even co-infecting human beings with IAV, which is a serious threat to human public health. As of yet, no specific antiviral drug has been discovered for SARS-CoV-2. This requires deeper understandings of the molecular mechanisms of SARS-CoV-2-host interaction, to explore antiviral drug targets and provide theoretical basis for developing anti-SARS-CoV-2 drugs. This article discussed IAV, which has been comprehensively studied and is expected to provide the most important reference value for the SARS-CoV-2 study apart from members of the Coronaviridae family. We wish to establish a theoretical system for the studies on virus-host interaction. Previous studies have shown that host PRRs recognize RNAs of IAV or SARS-CoV-2 and then activate innate immune signaling pathways to induce the expression of host restriction factors, such as ISGs, to ultimately inhibit viral replication. Meanwhile, viruses have also evolved various regulatory mechanisms to antagonize host innate immunity at transcriptional, translational, post-translational modification, and epigenetic levels. Besides, viruses can hijack supportive host factors for their replication. Notably, the race between host antiviral innate immunity and viral antagonism of host innate immunity forms virus-host interaction networks. Additionally, the viral replication cycle is co-regulated by proteins, ncRNAs, sugars, lipids, hormones, and inorganic salts. Given this, we updated the mappings of antiviral drug targets based on virus-host interaction networks and proposed an innovative idea that virus-host interaction networks as new antiviral drug targets for IAV and SARS-CoV-2 from the perspectives of viral immunology and systems biology.

KEYWORDS:

• IAV
• SARS-CoV-2
• virus-host interactions
• replication cycle
• host innate immunity
• antiviral drug targets
• Omicron

Acknowledgments

The authors thank the members of the Ping laboratory for helpful discussions. Na Chen performed the systematic literature review and wrote the manuscript. Baoge Zhang, Lulu Deng, and Bing Liang revised the manuscript. Jihui Ping organized and provided the frame for the manuscript and critically revised the manuscript. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

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Funding

This work was supported by the National Key Research and Development Programme of China (Grant number: 2021YFD1800205), National Natural Science Foundation of China (Grant number: 31772775), State Key Laboratory of Veterinary Biotechnology (SKLVBF202103), the Specialized Fund for the Basic Research Operating Expenses Programme of Central College (Grant number: KYZ201726) and the Priority Academic Programme Development of Jiangsu Higher Education Institutions (PAPD).