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All Studies   Meta Analysis    Recent:   

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

Zhang et al., Pathogens, doi:10.3390/pathogens13010075
Jan 2024  
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Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020
 
*, now known with p < 0.00000000001 from 84 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,800+ studies for 60+ treatments. c19early.org
Review of the ORF3a protein of SARS-CoV-2 as a therapeutic target for COVID-19 due to its role in viral pathogenesis, triggering cytokine storms, tissue damage, and disease severity. Existing drugs doxycycline, metformin, and ibrutinib are proposed for inhibiting ORF3a-mediated pathways, and authors identify chlorin e6 and TmPyP4 as promising inhibitors.
Reviews covering metformin for COVID-19 include De Jesús-González, Halma, Petakh, Tseng, Zhang.
Zhang et al., 14 Jan 2024, USA, peer-reviewed, 10 authors. Contact: rzhao@som.umaryland.edu (corresponding author), jiantao.zhang@som.umaryland.edu, chenyu.zhang@som.umaryland.edu, hom@rx.umaryland.edu, fxue@rx.umaryland.edu, mnasr@niaid.nih.gov, vgerzanich@som.umaryland.edu, msimard@som.umaryland.edu, zhangyj@umd.edu, qiyi.tang@howard.edu.
This PaperMetforminAll
SARS-CoV-2 ORF3a Protein as a Therapeutic Target against COVID-19 and Long-Term Post-Infection Effects
Jiantao Zhang, Kellie Hom, Chenyu Zhang, Mohamed Nasr, Volodymyr Gerzanich, Yanjin Zhang, Qiyi Tang, Fengtian Xue, J Marc Simard, Richard Y Zhao
Pathogens, doi:10.3390/pathogens13010075
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.
Author Contributions: Conceptualization, R.Y.Z.; writing-original draft preparation, R.Y.Z. and J.Z.; writing-review and editing, J.M.S., F.X., Q.T., Y.Z., V.G., M.N., K.H. and C.Z.; visualization, J.Z.; supervision, R.Y.Z.; project administration, R.Y.Z.; funding acquisition, R.Y.Z., J.M.S., Q.T. and V.G. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
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