Evidence map›Paper›PMID 38251382›Full record

ReviewPathogens (Basel, Switzerland)2024

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

Open access · goldAbstract readReview
In one paragraph

Review in Pathogens (Basel, Switzerland), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
5.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Jiantao ZhangDepartment of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.ORCID 0000-0002-2875-9743
Kellie HomDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
Chenyu ZhangDepartment of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Mohamed NasrDrug Development and Clinical Sciences Branch, Division of AIDS, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-3322-3716
Volodymyr GerzanichDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.ORCID 0000-0002-6714-1946
Yanjin ZhangDepartment of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.ORCID 0000-0002-5847-3260
Qiyi TangDepartment of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA.ORCID 0000-0002-6487-2356
Fengtian XueDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
J Marc SimardDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.ORCID 0000-0002-5373-1988
Richard Y ZhaoDepartment of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.ORCID 0000-0003-3424-2852
University of Maryland, Baltimore · USHoward University · USNational Institutes of Health · USUniversity of Maryland, College Park · US

Funding

Sleep Disorders in Adults with Sickle Cell Disease: Frequency, Associations with Cardiovascular and Pain Indicators, and Responses to TreatmentU54MD007597 · NIMHD · HOWARD UNIVERSITY · PI GEORGES E. HADDAD · 2019 to 2026
$37.7M
PROTEOMICS CORE FACILITYG12MD007597 · NIMHD · HOWARD UNIVERSITY · PI SOUTHERLAND, WILLIAM M. · 2012 to 2018
$14.8M
Sulfonylurea receptor 1 (SUR1)- A novel therapeutic target in ischemic strokeR01HL082517 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI SIMARD, J. MARC · 2006 to 2021
$5.6M
Molecular Neuro-pathogenesis of Congenital Cytomegalovirus InfectionSC1AI112785 · NIAID · PONCE SCHOOL OF MEDICINE · PI TANG, QIYI · 2014 to 2021
$2.8M
Fn14, non-canonical NF-kappaB and downstream signaling in neuropathic painR01NS105633 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI SIMARD, J. MARC · 2018 to 2022
$1.9M
Non-canonical NF-kappaB signaling and Sur1-Trpm4 in traumatic brain injuryR01NS102589 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI SIMARD, J. MARC · 2017 to 2021
$1.7M
Sur1-Trpm4 regulation of the pro-inflammatory astrocytic secretome in EAER01NS107262 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI GERZANICH, VLADIMIR · 2020 to 2024
$1.7M
A Novel and High Throughput System for Drug Discovery and Testing on Multidrug Resistant HIV-1 ProteasesR01GM127212 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE · PI ZHAO, RICHARD YUQI · 2017 to 2018
$603k
Rapid Phenotyping of the ZIKV GenomeR21AI129369 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI ZHAO, RICHARD YUQI · 2017 to 2018
$425k
A Novel and High Throughput System for Drug Discovery and Testing on Multidrug Resistant HIV-1 ProteasesR01AI150459 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI ZHAO, RICHARD YUQI · 2019 to 2019
$301k
Viral Protein R (Vpr) in HIV-associated Brain Neuroinflammation and NeurotoxicityI01BX004652 · VA · BALTIMORE VA MEDICAL CENTER · PI J. Marc Simard, RICHARD YUQI ZHAO · 2020 to 2026
–
Therapeutic potential and the critical site of action of non-addicting glibenclamide in neuropathic painI01RX003060 · VA · BALTIMORE VA MEDICAL CENTER · PI SIMARD, J. MARC · 2020 to 2023
–
BLRD VA I01 BX004652NHLBI NIH HHS R01 HL082517NIAID NIH HHS R01 AI150459NIAID NIH HHS R21 AI129369NIAID NIH HHS SC1 AI112785NIGMS NIH HHS R01 GM127212NIMHD NIH HHS G12 MD007597NIMHD NIH HHS G12MD007597NIMHD NIH HHS U54 MD007597NINDS NIH HHS NS102589NINDS NIH HHS NS105633NINDS NIH HHS NS107262NINDS NIH HHS R01 NS102589NINDS NIH HHS R01 NS105633NINDS NIH HHS R01 NS107262RRD VA I01 RX003060
6 · The paper itself

Abstract

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.

Indexed as

Antiviral AgentsCOVID-19SARS-CoV-2Viroporin ProteinsCOVID-19 Drug TreatmentHumansVirus ReplicationAntiviral AgentsORF3a protein, SARS-CoV-2Viroporin Proteinsantiviral targetCOVID-19cytokine stormhigh-throughput screeningkidney injuryneuroinflammationORF3aSARS-CoV-2viral pathogenesis

Identifiers

PMID38251382
PMCPMC10819734
OpenAlexW4390877664

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.