Targeting Viral ORF3a Protein: A New Approach to Mitigate COVID-19 Induced Immune Cell Apoptosis and Associated Respiratory Complications

Treeza, Minu; Augustine, Sanu; Mathew, Aparna Ann; KANTHLAL, SK; Panonnummal, Rajitha

doi:10.34172/apb.2023.069

Cited by 2 publications

(1 citation statement)

References 98 publications

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“…The multifaceted roles of ORF3a in viral pathogenesis, cytokine storm induction, and tissue damage associated with severe COVID-19 and long-term complications make it an attractive target for potential antiviral drugs or treatments [18,120,121]. Exploring inhibitor drugs against ORF3a protein involves several strategic approaches (Figure 1B).…”

Section: Discovery and Development Of Inhibitor Drugs Targeting Orf3a...mentioning

confidence: 99%

SARS-CoV-2 ORF3a Protein as a Therapeutic Target against COVID-19 and Long-Term Post-Infection Effects

Zhang,

Hom,

Zhang

et al. 2024

Pathogens

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The COVID-19 pandemic caused by SARS-CoV-2 has posed unparalleled challenges due to its rapid transmission, ability to mutate, high mortality and morbidity, and enduring health complications. Vaccines have exhibited effectiveness, but their efficacy diminishes over time while new variants continue to emerge. Antiviral medications offer a viable alternative, but their success has been inconsistent. Therefore, there remains an ongoing need to identify innovative antiviral drugs for treating COVID-19 and its post-infection complications. The ORF3a (open reading frame 3a) protein found in SARS-CoV-2, represents a promising target for antiviral treatment due to its multifaceted role in viral pathogenesis, cytokine storms, disease severity, and mortality. ORF3a contributes significantly to viral pathogenesis by facilitating viral assembly and release, essential processes in the viral life cycle, while also suppressing the body’s antiviral responses, thus aiding viral replication. ORF3a also has been implicated in triggering excessive inflammation, characterized by NF-κB-mediated cytokine production, ultimately leading to apoptotic cell death and tissue damage in the lungs, kidneys, and the central nervous system. Additionally, ORF3a triggers the activation of the NLRP3 inflammasome, inciting a cytokine storm, which is a major contributor to the severity of the disease and subsequent mortality. As with the spike protein, ORF3a also undergoes mutations, and certain mutant variants correlate with heightened disease severity in COVID-19. These mutations may influence viral replication and host cellular inflammatory responses. While establishing a direct link between ORF3a and mortality is difficult, its involvement in promoting inflammation and exacerbating disease severity likely contributes to higher mortality rates in severe COVID-19 cases. This review offers a comprehensive and detailed exploration of ORF3a’s potential as an innovative antiviral drug target. Additionally, we outline potential strategies for discovering and developing ORF3a inhibitor drugs to counteract its harmful effects, alleviate tissue damage, and reduce the severity of COVID-19 and its lingering complications.

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Section: Discovery and Development Of Inhibitor Drugs Targeting Orf3a...mentioning

confidence: 99%

SARS-CoV-2 ORF3a Protein as a Therapeutic Target against COVID-19 and Long-Term Post-Infection Effects

Zhang,

Hom,

Zhang

et al. 2024

Pathogens

View full text Add to dashboard Cite

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Avian Coronavirus Infectious Bronchitis Virus Activates Mitochondria-Mediated Apoptosis Pathway and Affects Viral Replication by Inducing Reactive Oxygen Species Production in Chicken HD11 Cells

Han,

Huang,

Hao

2024

Biology

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Infectious bronchitis virus (IBV), a coronavirus that causes severe respiratory and gastrointestinal illness in poultry, leads to substantial economic losses. According to earlier research, IBV infection causes chicken macrophage HD11 cells to undergo cell apoptosis. Reactive oxygen species (ROS) and the IBV-activated intrinsic apoptotic signaling pathway were examined in this work. The findings demonstrate that IBV infection causes ROS to accumulate. Moreover, IBV infection decreased the mitochondrial transmembrane potential in HD11 cells, which could be blocked by ROS antioxidants (PDTC and NAC). The two antioxidants significantly affected the expression of Bcl-2 and Bax and further inhibited the activation of caspase-3 and apoptosis in HD11 cells. Additionally, IBV replication was decreased by blocking ROS accumulation. Pretreating HD11 cells with ammonium chloride (NH4Cl) prevented IBV from entering the cells and reduced the oxidative stress which IBV causes. The ability to accumulate ROS was also lost in UV-inactivated IBV. The IBV N protein induces cell apoptosis through the activation of ROS. These findings provide an explanation for the processes of IBV infection in immune cells by indicating that IBV-induced ROS generation triggers cell apoptosis in HD11 cells.

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Targeting Viral ORF3a Protein: A New Approach to Mitigate COVID-19 Induced Immune Cell Apoptosis and Associated Respiratory Complications

Cited by 2 publications

References 98 publications

SARS-CoV-2 ORF3a Protein as a Therapeutic Target against COVID-19 and Long-Term Post-Infection Effects

SARS-CoV-2 ORF3a Protein as a Therapeutic Target against COVID-19 and Long-Term Post-Infection Effects

Avian Coronavirus Infectious Bronchitis Virus Activates Mitochondria-Mediated Apoptosis Pathway and Affects Viral Replication by Inducing Reactive Oxygen Species Production in Chicken HD11 Cells

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