Virus-host interactomics: new insights and opportunities for antiviral drug discovery

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.

Centrality in the host–pathogen interactome is associated with pathogen fitness during infection

“…Finally, our observations have important implications in drug design141516. Antimicrobial development has focused on essential proteins (mainly enzymes) required for the pathogen to survive in culture (that is, in vitro ).…”

The Curtius Rearrangement: Applications in Modern Drug Discovery and Medicinal Chemistry

“…The advances of molecular biology and new technologies have a tremendous impact on the development of novel and effective antiviral therapies for the treatment of most viral infections . The majority of today′s approved antiviral drugs specifically target proteins critical to viral replication . Thus, protein structure‐based drug design plays a very important role in developing many structural classes of effective antiviral drugs.…”

Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection

“…To date, these advances in proteomic-based approaches have paved the way for the identification of an impressive number of virus-host protein associations that otherwise may not have been uncovered using more traditional approaches. In fact, these studies have provided the foundation for publically accessible databases, which currently contain over 5000 curated and non-redundant protein interactions between components of the virus and of the permissive host cell [121][122][123][124][125][126][127]. These valuable repositories include the Database of Interacting Proteins [127], VirHostNet [124,125], VirusMentha [123], IntAct-MINT, and Uniprot [122].…”