Abstract
The current therapeutic arsenal against viral infections remains limited, with often poor efficacy and incomplete coverage, and appears inadequate to face the emergence of drug resistance. Our understanding of viral biology and pathophysiology and our ability to develop a more effective antiviral arsenal would greatly benefit from a more comprehensive picture of the events that lead to viral replication and associated symptoms. Towards this goal, the construction of virus-host interactomes is instrumental, mainly relying on the assumption that a viral infection at the cellular level can be viewed as a number of perturbations introduced into the host protein network when viral proteins make new connections and disrupt existing ones. Here, we review advances in interactomic approaches for viral infections, focusing on high-throughput screening (HTS) technologies and on the generation of high-quality datasets. We show how these are already beginning to offer intriguing perspectives in terms of virus-host cell biology and the control of cellular functions, and we conclude by offering a summary of the current situation regarding the potential development of host-oriented antiviral therapeutics.
Highlights
Conventional drug therapies against human viruses mainly target viral enzymes (Table 1)
Antiviral drug discovery is beginning to explore the possibility to develop host-oriented molecules acting on cellular functions that are essential for viruses to replicate [4]
As the vast majority of cellular functions is supported by interacting proteins, the manipulation of cellular processes by viruses mainly results from physical interactions between viral and host proteins [5]
Summary
Conventional drug therapies against human viruses mainly target viral enzymes (Table 1). After five to ten passages, no reduction of the antiviral effect was observed using host-oriented molecules (a MEK inhibitor [72], inhibitors of NF-κB [3,73] or an inhibitor of Rac1 [74]), whereas the use of the direct-acting drugs oseltamivir or amantadine (the two classes of approved drugs for the treatment of influenza) led to rapid emergence of resistant variants This indicates that the virus cannot adapt to a situation where cellular functions that are essential for its replication become less accessible and further suggests that targeting the host confers a greater barrier to the development of viral resistance. This potential has been accelerating since the first high-throughput screenings for VH PPIs
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