Dear Colleagues,

Over the past twenty years, the “structure–function” paradigm has been challenged by the discovery of intrinsically disordered proteins and regions (IDPs and IDRs, respectively), which are proteins/regions that are devoid of a unique tertiary structure under the conditions of physiological pH and salinity and that do not have binding partners. Among these IDPs or hybrid proteins with ordered domains and functional IDRs are viral proteins, such as the measles virus nucleoprotein and phosphoprotein, which possess long (>300 residues) IDRs. Since 2002, Longhi’s group has played a pioneering role in the discovery of disorders in these proteins and has extended these studies to show the prevalence of these intrinsic disorders  in a wide range of viruses, such as Nipah and Hendra, two biosafety level 4 human pathogens. This discovery opened the field to a new area of structural virology that is focused on elucidating the benefits of structural disorders. From the work of Sonia Longhi’s group, it has become clear that the functional role of structural disorders resides in enabling the virus to establish multiple interactions in spite of a small genome, allowing one single gene product to drive many different interactions, leading to multiple biological outcomes and functions. In addition, disorders allow the virus to handle overlapping reading frames, a common feature of viruses. More recently, it has become evident that disorders also mediate phase separation and liquid–liquid phase transition phenomena, which underlie the formation of viral factories in members of the Mononegavirales family as well as other viruses and membraneless organelles in cellular organisms. These condensates allow for the fine spatio-temporal regulation of cellular activities. They can undergo a “maturation” process to become gelified and/or solid condensates that are capable of nucleating amyloid-like fibers. The ability of viral proteins to undergo functional phase separation and fibrillation opens up the potential use of fibrillation inhibitors as antiviral therapeutics.

Dr. Sonia Longhi, one of the pioneers in the field of IDPs and of “unstructured” virology, received an HDR in Structural Virology from the University of Aix-Marseille I in 2003. Her scientific focus is on health-relevant IDPs and the mechanistic and functional aspects of their heterotypic and homotypic interactions. To date, she has authored 145 scientific publications and has edited a book on the nucleoprotein of the measles virus. She also co-edited (with Prof. Vladimir Uversky) a book on experimental approaches to characterize IDPs and a book on structural disorders within viral proteins (Wiley). Today, twenty years later, to celebrate her many contributions to IDP and the field of “unstructured” virology, we hope that Biomolecules publish this Special Issue in her honor. This Special Issue aims to present the state of the art and invites contributions, especially from those researchers who have known Dr. Sonia Longhi personally.

Prof. Dr. Elisar Barbar
Dr. Nathalie Sibille
Prof. Dr. Vladimir N. Uversky
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• binding promiscuity
• conformational ensemble
• disorder in viral proteins
• disorder in viruses
• disorder-to-order transition
• folding upon binding
• innate immunity
• intrinsic disorder in virus antigen
• Intrinsically Disordered Proteins (IDPs)
• Intrinsically Disordered Regions (IDPs)
• Liquid-liquid phase separation
• order-to-disorder transition
• protein-protein interactions
• reading frame
• structural disorder
• structural plasticity
• unstructured virology
• viral factories
• virus-host interaction