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Home » Study reveals the role of ORF6 protein in COVID-19 symptoms

Study reveals the role of ORF6 protein in COVID-19 symptoms

In a recent study published in the Journal of Physical Chemistry Letters, researchers from Kanazawa University utilized high-speed atomic force microscopy (HS-AFM) to investigate the potential role of the open reading frame 6 (ORF6) in COVID-19 symptoms.

Despite a global slowdown in the spread of SARS-CoV-2, the virus causing COVID-19, cases persist, prompting researchers to delve into the mechanisms sustaining the virus in the human body. Accessory , including ORF6, play a crucial role in the virus's ability to thrive within the host.

Previous research indicated that ORF6 might interfere with interferon 1 (IFN-I), a key immune system protein, potentially explaining asymptomatic infections. Additionally, evidence suggested that ORF6 contributes to protein retention in the cell's cytoplasm and disrupts mRNA transport, hindering IFN-I signaling. However, the precise mechanism of this protein's actions remained unclear.

To unravel these mechanisms, the scientists employed various software programs and nuclear magnetic resonance measurements to identify intrinsically disordered regions within ORF6. While algorithms like AlphaFold2 are effective in determining protein folding, the presence of disordered regions limits their utility. Instead, the researchers turned to HS-AFM, capable of detecting structures by analyzing sample topography.

HS-AFM revealed that ORF6 predominantly forms ellipsoidal filaments of oligomers—repeating molecular units in shorter strings than polymers. The filaments' length and circumference varied with temperature, suggesting a potential benefit from fever in producing larger filaments. Moreover, lipid substrates encouraged the formation of larger oligomers.

The rapid image capture of HS-AFM provided insights into the dynamics of ORF6 behavior, including circular motion, protein assembly, and flipping. Computer analysis further unveiled the filaments' propensity to aggregate into amyloids, akin to those found in , potentially complicating COVID-19 symptoms. The researchers noted that this aggregation effectively sequesters host proteins, particularly those involved in IFN-I signaling.

Notably, these filaments disintegrate in the presence of certain substances, leading the researchers to conclude that hydrophobic interactions largely hold the protein together. The study suggests exploring potential druggable candidates that disrupt hydrophobic interactions to dissociate ORF6 aggregates, offering avenues for therapeutic interventions in COVID-19 management and treatment.

Source: Kanazawa University

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