ReviewThe Journal of biological chemistry
Priming of SARS-CoV-2 S protein by several membrane-bound serine proteinases could explain enhanced viral infectivity and systemic COVID-19 infection.
Review in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Pooled it
- TMPRSS2-induced Golgi disruption restricts the incorporation of virus envelope glycoproteins into virions.EMBO reports · 2026Article
- Large Library Docking and Biophysical Analysis of Small-Molecule TMPRSS2 Inhibitors.Journal of medicinal chemistry · 2025Article
- A survey of SARS-CoV-2 tropism.Infectious diseases & immunity · 2025Review
- Evolution of the SARS-CoV-2 spike protein in utilizing host transmembrane serine proteases.iScience · 2025Article
- TMPRSS2: A Key Host Factor in SARS-CoV-2 Infection and Potential Therapeutic Target.Medeniyet medical journal · 2025Article
- SARS-CoV2 infection triggers inflammatory conditions and astrogliosis-related gene expression in long-term human cortical organoids.Stem cells (Dayton, Ohio) · 2025Article
- Natural and Synthetic Coumarins as Potential Drug Candidates against SARS-CoV-2/COVID-19.Current medicinal chemistry · 2025Review
- Lactoferrin Binds through Its N-Terminus to the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Comprehensive Review of COVID-19: Epidemiology, Pathogenesis, Advancement in Diagnostic and Detection Techniques, and Post-Pandemic Treatment Strategies.International journal of molecular sciences · 2024Review
- Efficacy of host cell serine protease inhibitor MM3122 against SARS-CoV-2 for treatment and prevention of COVID-19.Journal of virology · 2024Article
- Seroprevalence of SARS-CoV-2 and Hepatitis B Virus Coinfections among Ethiopians with Acute Leukemia.Cancers · 2024Article
- The Inhibition of Serine Proteases by Serpins Is Augmented by Negatively Charged Heparin: A Concise Review of Some Clinically Relevant Interactions.International journal of molecular sciences · 2024Review
- A novel approach to designing viral precision vaccines applied to SARS-CoV-2.Frontiers in cellular and infection microbiology · 2024Article
- Bacterial Proteases as Potentially Exploitable Modulators of SARS-CoV-2 Infection: Logic from the Literature, Informatics, and Inspiration from the Dog.Biotech (Basel (Switzerland)) · 2023Article
- Impact of COVID-19 on thyroid gland functions with reference to Graves' disease: A systematic review.Journal of family medicine and primary care · 2023Review
- Type II Transmembrane Serine Proteases as Modulators in Adipose Tissue Phenotype and Function.Biomedicines · 2023Review
- Article
- Time to Kill and Time to Heal: The Multifaceted Role of Lactoferrin and Lactoferricin in Host Defense.Pharmaceutics · 2023Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ongoing COVID-19 pandemic has already caused over a million deaths worldwide, and this death toll will be much higher before effective treatments and vaccines are available. The causative agent of the disease, the coronavirus SARS-CoV-2, shows important similarities with the previously emerged SARS-CoV-1, but also striking differences. First, SARS-CoV-2 possesses a significantly higher transmission rate and infectivity than SARS-CoV-1 and has infected in a few months over 60 million people. Moreover, COVID-19 has a systemic character, as in addition to the lungs, it also affects the heart, liver, and kidneys among other organs of the patients and causes frequent thrombotic and neurological complications. In fact, the term "viral sepsis" has been recently coined to describe the clinical observations. Here I review current structure-function information on the viral spike proteins and the membrane fusion process to provide plausible explanations for these observations. I hypothesize that several membrane-associated serine proteinases (MASPs), in synergy with or in place of TMPRSS2, contribute to activate the SARS-CoV-2 spike protein. Relative concentrations of the attachment receptor, ACE2, MASPs, their endogenous inhibitors (the Kunitz-type transmembrane inhibitors, HAI-1/SPINT1 and HAI-2/SPINT2, as well as major circulating serpins) would determine the infection rate of host cells. The exclusive or predominant expression of major MASPs in specific human organs suggests a direct role of these proteinases in e.g., heart infection and myocardial injury, liver dysfunction, kidney damage, as well as neurological complications. Thorough consideration of these factors could have a positive impact on the control of the current COVID-19 pandemic.
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Registered trials
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.