Host-Targeting Antivirals: From Mechanism to Intervention
A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".
Deadline for manuscript submissions: 28 February 2026 | Viewed by 28
Special Issue Editor
Interests: both human and highly pathogenic avian influenza viruses
Special Issues, Collections and Topics in MDPI journals
Special Issue Information
Dear Colleagues,
the constant emergence and re-emergence of viral pathogens continue to pose major challenges to global public health. The COVID-19 pandemic, alongside periodic outbreaks of influenza, Ebola, Zika, Mpox, and other viral diseases, has highlighted the urgent need for innovative therapeutic approaches that can overcome the limitations of traditional antiviral strategies. As we are confronted by increasing viral diversity, rapid mutation rates, and the inevitable development of drug resistance, we must pursue the development of novel antivirals.
Host-targeting antivirals (HTAs) represent one of the most promising and underexplored approaches in contemporary antiviral research. Unlike conventional direct-acting antivirals (DAAs), which specifically target viral proteins, HTAs disrupt essential host cellular processes that viruses hijack for their replication and pathogenesis. As different members of a virus family have common dependencies on cellular factors and mechanisms, HTAs have the potential to act as broad-spectrum antivirals and may represent versatile therapeutics against emerging and yet unknown viral threats. This fundamental shift from virus-centric to host-centric therapeutic approaches offers compelling advantages in addressing the most pressing challenges in antiviral therapy: the rapid emergence of drug resistance, limited broad-spectrum efficacy, and the protracted timeline required for developing pathogen-specific treatments.
Furthermore, dual-targeting approaches, where single compounds simultaneously disrupt host pathways essential for viral replication, could potentially enhance antiviral efficacy and slow the development of resistance. In contrast to DAAs, which require years of development, HTAs could provide immediate therapeutic options, potentially preventing epidemics from progressing to pandemic proportions.
Our ability to identify and characterize virus/host interactions at unprecedented scales through high-throughput screening technologies, CRISPR-based functional genomics, proteomics approaches, and artificial intelligence-driven drug repurposing strategies has accelerated the discovery of novel host targets and expanded the repertoire of available HTA candidates. Moreover, many host-targeting compounds are repurposed drugs with established safety profiles, potentially reducing development timelines and overcoming regulatory barriers.
Despite these promising developments, significant research challenges remain, i.e., potential cytotoxicity and viral resistance through alternative mechanisms. Understanding these resistance mechanisms and developing strategies to circumvent them represent a critical research priority.
The expansion of HTA research requires interdisciplinary collaboration spanning virology, immunology, systems biology, medicinal chemistry, and computational sciences. We therefore invite the research community to contribute to this Special Issue.
Prof. Dr. Stephan Pleschka
Guest Editor
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Keywords
- host-targeting antivirals
- host receptors
- signaling pathways
- metabolic networks
- transcription factors
- treatment
- clinical intervention practice
- preclinical data
- intervention strategy design
- mechanism
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