Structural disorder in the proteome and interactome of Alkhurma virus (ALKV)

Abstract

Infection by the Alkhurma virus (ALKV) leading to the Alkhurma hemorrhagic fever is a common thread in Saudi Arabia, with no efficient treatment or prevention available as of yet. Although the rational drug design traditionally uses information on known 3D structures of viral proteins, intrinsically disordered proteins (i.e., functional proteins that do not possess unique 3D structures), with their multitude of disorder-dependent functions, are crucial for the biology of viruses. Here, viruses utilize disordered regions in their invasion of the host organisms and in hijacking and repurposing of different host systems. Furthermore, the ability of viruses to efficiently adjust and accommodate to their hostile habitats is also intrinsic disorderdependent. However, little is currently known on the level of penetrance and functional utilization of intrinsic disorder in the ALKV proteome. To fill this gap, we used here multiple computational tools to evaluate the abundance of intrinsic disorder in the ALKV genome polyprotein. We also analyzed the peculiarities of intrinsic disorder predisposition of the individual viral proteins, as well as human proteins known to be engaged in interaction with the ALKV proteins. Special attention was paid to finding a correlation between protein functionality and structural disorder. To the best of our knowledge, this work represents the first systematic study of the intrinsic disorder status of ALKV proteome and interactome.Electronic supplementary material The online version of this article (https ://doi.

Understanding the penetrance of intrinsic protein disorder in rotavirus proteome

“…In general, viruses, due to their limited protein-coding capacity, could gain several functional advantages from IDPs/IDPRs in terms of assembly of replication complexes involving a large number of viral and host proteins and survival in extreme host environments [12]. In recent studies, we have shown the prevalence of IDPs/IDPRs and their functional significance in Zika virus (ZIKV) and Chikungunya virus (CHIKV) [13,14], as well as in Hepatitis C virus (HCV) [15], human immunodeficiency virus-1 (HIV-1) [16], various human papillomaviruses (HPVs) [17], respiratory syncytial virus (RSV) [18], Dengue virus [19], MERS-CoV [20], and Alkhurma virus (ALKV) [21].…”

Zika and Flavivirus Shell Disorder: Virulence and Fetal Morbidity

“…The penetrance of disorder in the proteins from flaviviruses and ZIKV has already been analyzed [23,24,25]. The abundance and specific functionality of intrinsically disordered proteins in viral proteomes in general have been considered in several large-scale computational studies [26,27] and have been specifically analyzed for human papillomaviruses [28,29], different strains of the influenza virus [30], human immunodeficiency virus type -1 (HIV-1) [31], human hepatitis C virus [32,33], Dengue virus [34], respiratory syncytial virus [35], Chikungunya virus [36], and Alkhurma virus [37]. Furthermore, previous studies have found correlations between virulence and the shell disorder of DENV and flaviviruses, although the sets used in those studies did not include ZIKV proteins [2,14].…”

Drugs, host proteins and viral proteins: how their promiscuities shape antiviral design

“…(2019) reported IDRs rich in MoRFs in several structural and non‐structural proteins of human T‐lymphotropic virus type‐1, including those involved in virus replication and genomic RNA binding. Similar results on the role of IDRs present in the viral proteomes have been reported for zika virus (Giri et al ., 2016; Mishra, Uversky, & Giri, 2018), chikungunya virus (Singh et al ., 2018), HPVs (Uversky et al ., 2006), dengue virus (Meng et al ., 2015), respiratory syncytial virus (Whelan et al ., 2016) and alkhurma virus (Redwan, Aljaddawi, & Uversky, 2019). Cook et al .…”