tetano
Editor, Senior Moderator
Front Chem
. 2025 Jun 11:13:1597656.
doi: 10.3389/fchem.2025.1597656. eCollection 2025. The role of intrinsically disordered regions of SARS-CoV-2 nucleocapsid and non-structural protein 1 proteins
Getasew Shitaye[SUP] 1 2 [/SUP], Nataliia Ventserova[SUP] 1 [/SUP], Gianluca D'Abrosca[SUP] 3 [/SUP], Martina Dragone[SUP] 1 [/SUP], Eunice Wairimu Maina[SUP] 1 [/SUP], Roberto Fattorusso[SUP] 1 [/SUP], Rosa Iacovino[SUP] 1 [/SUP], Luigi Russo[SUP] 1 [/SUP], Carla Isernia[SUP] 1 4 [/SUP], Gaetano Malgieri[SUP] 1 4 [/SUP]
Affiliations
Virus survival inside the host cell depends on the intricate mechanisms that recruit proteins involved in the arms race. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) proteome exhibits important levels of structural order. However, some of the SARS-CoV-2 proteins, such as the Nucleocapsid (N) and Non-structural protein 1 (Nsp1), contain a considerably significant amount of intrinsically disordered regions (IDRs) that play indispensable roles in the intra-viral and virus-host interaction. Here, focusing on proteins that contain a relevant percentage of IDRs, we discuss experimental and computational studies sought to support IDRs as a key player in the interplay with ordered domains, the biological role as potential origin for variants of SARS-CoV-2, and their association with virus transmissibility. Furthermore, we also highlight the potential involvement of IDRs in the viral-host protein interaction and host cellular machinery. Thus, shading lights on the dark proteome of the virus and looking for therapeutic approaches beyond the classic structure-function paradigm may contribute to the efforts sparking the quest for therapeutics.
Keywords: SARS-COV-2 variants; coronaviruses; host-viral interactions; intrinsically disordered proteins; protein-protein interactions.
. 2025 Jun 11:13:1597656.
doi: 10.3389/fchem.2025.1597656. eCollection 2025. The role of intrinsically disordered regions of SARS-CoV-2 nucleocapsid and non-structural protein 1 proteins
Getasew Shitaye[SUP] 1 2 [/SUP], Nataliia Ventserova[SUP] 1 [/SUP], Gianluca D'Abrosca[SUP] 3 [/SUP], Martina Dragone[SUP] 1 [/SUP], Eunice Wairimu Maina[SUP] 1 [/SUP], Roberto Fattorusso[SUP] 1 [/SUP], Rosa Iacovino[SUP] 1 [/SUP], Luigi Russo[SUP] 1 [/SUP], Carla Isernia[SUP] 1 4 [/SUP], Gaetano Malgieri[SUP] 1 4 [/SUP]
Affiliations
- PMID: 40568634
- PMCID: PMC12187666
- DOI: 10.3389/fchem.2025.1597656
Virus survival inside the host cell depends on the intricate mechanisms that recruit proteins involved in the arms race. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) proteome exhibits important levels of structural order. However, some of the SARS-CoV-2 proteins, such as the Nucleocapsid (N) and Non-structural protein 1 (Nsp1), contain a considerably significant amount of intrinsically disordered regions (IDRs) that play indispensable roles in the intra-viral and virus-host interaction. Here, focusing on proteins that contain a relevant percentage of IDRs, we discuss experimental and computational studies sought to support IDRs as a key player in the interplay with ordered domains, the biological role as potential origin for variants of SARS-CoV-2, and their association with virus transmissibility. Furthermore, we also highlight the potential involvement of IDRs in the viral-host protein interaction and host cellular machinery. Thus, shading lights on the dark proteome of the virus and looking for therapeutic approaches beyond the classic structure-function paradigm may contribute to the efforts sparking the quest for therapeutics.
Keywords: SARS-COV-2 variants; coronaviruses; host-viral interactions; intrinsically disordered proteins; protein-protein interactions.