Back to Search
Start Over
Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming
- Source :
- Molecules, Volume 25, Issue 10, Molecules, Vol 25, Iss 2424, p 2424 (2020)
- Publication Year :
- 2020
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2020.
-
Abstract
- Processing of certain viral proteins and bacterial toxins by host serine proteases is a frequent and critical step in virulence. The coronavirus spike glycoprotein contains three (S1, S2, and S2&prime<br />) cleavage sites that are processed by human host proteases. The exact nature of these cleavage sites, and their respective processing proteases, can determine whether the virus can cross species and the level of pathogenicity. Recent comparisons of the genomes of the highly pathogenic SARS-CoV2 and MERS-CoV, with less pathogenic strains (e.g., Bat-RaTG13, the bat homologue of SARS-CoV2) identified possible mutations in the receptor binding domain and in the S1 and S2&prime<br />cleavage sites of their spike glycoprotein. However, there remains some confusion on the relative roles of the possible serine proteases involved for priming. Using anthrax toxin as a model system, we show that in vivo inhibition of priming by pan-active serine protease inhibitors can be effective at suppressing toxicity. Hence, our studies should encourage further efforts in developing either pan-serine protease inhibitors or inhibitor cocktails to target SARS-CoV2 and potentially ward off future pandemics that could develop because of additional mutations in the S-protein priming sequence in coronaviruses.
- Subjects :
- Models, Molecular
COVID19
medicine.medical_treatment
viruses
Pharmaceutical Science
Priming (immunology)
medicine.disease_cause
Analytical Chemistry
Serine
Mice
0302 clinical medicine
Drug Delivery Systems
Drug Discovery
SARS-COV2
Coronavirus
chemistry.chemical_classification
0303 health sciences
Mice, Inbred BALB C
Chemistry (miscellaneous)
Spike Glycoprotein, Coronavirus
Molecular Medicine
Female
Anthrax toxin
Coronavirus Infections
furin
Proteases
Serine Proteinase Inhibitors
Bacterial Toxins
Pneumonia, Viral
Virulence
Biology
Antiviral Agents
Article
Microbiology
lcsh:QD241-441
03 medical and health sciences
Betacoronavirus
protecting antigen
lcsh:Organic chemistry
medicine
Animals
Humans
Physical and Theoretical Chemistry
Pandemics
TMPRSS2
030304 developmental biology
Antigens, Bacterial
Protease
Binding Sites
SARS-CoV-2
Organic Chemistry
fungi
COVID-19
RAW 264.7 Cells
chemistry
Serine Proteases
Glycoprotein
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....e6a7761738bcdf7f0eb2b502ad0b2403
- Full Text :
- https://doi.org/10.3390/molecules25102424