On the Prevalence and Potential Functionality of an Intrinsic Disorder in the MERS-CoV Proteome

Abstract

Middle East respiratory syndrome is a severe respiratory illness caused by an infectious coronavirus. This virus is associated with a high mortality rate, but there is as of yet no effective vaccine or antibody available for human immunity/treatment. Drug design relies on understanding the 3D structures of viral proteins; however, arriving at such understanding is difficult for intrinsically disordered proteins, whose disorder-dependent functions are key to the virus’s biology. Disorder is suggested to provide viral proteins with highly flexible structures and diverse functions that are utilized when invading host organisms and adjusting to new habitats. To date, the functional roles of intrinsically disordered proteins in the mechanisms of MERS-CoV pathogenesis, transmission, and treatment remain unclear. In this study, we performed structural analysis to evaluate the abundance of intrinsic disorder in the MERS-CoV proteome and in individual proteins derived from the MERS-CoV genome. Moreover, we detected disordered protein binding regions, namely, molecular recognition features and short linear motifs. Studying disordered proteins/regions in MERS-CoV could contribute to unlocking the complex riddles of viral infection, exploitation strategies, and drug development approaches in the near future by making it possible to target these important (yet challenging) unstructured regions.

Hepatitis C Virus Infection and Intrinsic Disorder in the Signaling Pathways Induced by Toll-Like Receptors

“…These observations are in line with the well-known association between the protein intrinsic disorder and pathogenesis of various human diseases [ 81 , 207 , 208 , 209 , 210 , 211 , 212 ]. They also agree with the results of the comprehensive bioinformatics analyses of the prevalence of protein intrinsic disorder in various viruses such as human papillomaviruses (HPVs) [ 213 ], HCV [ 41 ], influenza viruses [ 214 ], HIV-1 [ 215 ], Dengue virus [ 216 ], respiratory syncytial virus (RSD) [ 217 ], Zika virus [ 218 , 219 ], Chikungunya virus [ 220 , 221 ], rotavirus [ 222 ], Japanese encephalitis virus [ 223 ], SARS-CoV-2 [ 224 , 225 ], human SARS and bat SARS-like coronaviruses [ 224 ], Middle East respiratory syndrome MERS coronavirus [ 226 , 227 ], and Chandipura virus [ 228 ] as well as in the interactomes of HPV [ 229 ] and HCV [ 40 ]. They are also supported by the results of the evaluation of intrinsic disorder in proteins involved in innate anti-viral immunity [ 230 ] and the comprehensive bioinformatics analysis of the global prevalence of intrinsic disorder in 6108 viral proteomes [ 231 ].…”

Protein Intrinsic Disorder and Evolvability of MERS-CoV

“…Previous studies highlighted the importance of the intrinsic disorder for the functionality of MERS-CoV proteins [17], and peculiarities of the intrinsic disorder distribution within the inner and outer shell proteins were attributed to the high oral-fecal transmission potential of MERS-CoV [18]. However, despite the fact that all MERS-CoV proteins were shown to contain functionally important intrinsically disordered regions, no information is available on the potential role of intrinsic disorder in the evolvability of this virus.…”