scholarly journals In Silico Prediction of SARS‐CoV ‐2 Main Protease Cleavage Sites

2021 ◽  
Author(s):  
Zheng Rong Yang
Keyword(s):  
In Silico ◽  
Cleavage Sites ◽  
In Silico Prediction ◽  
Protease Cleavage ◽  
Main Protease ◽  
Protease Cleavage Sites

scholarly journals PNPLA3 and TLL-1 polymorphisms affect disease severity in patients with COVID-19

2020 ◽  
Author(s):  
Stefania Grimaudo ◽  
Emanuele Amodio ◽  
Rosaria Maria Pipitone ◽  
Carmelo Massimo Maida ◽  
Stefano Pizzo ◽  
...  
Keyword(s):  
In Silico ◽  
Intensive Therapy ◽  
Cleavage Sites ◽  
Protein Cleavage ◽  
Protease Cleavage ◽  
Increased Risk ◽  
Specific Protease ◽  
Protease Cleavage Sites ◽  
Male Subjects ◽  
Affect Disease Severity

Abstract Introduction Albeit the pathogenesis of COVID-19 remains unclear, host’s genetic polymorphisms in genes infection and reinfection, inflammation, or immune stimulation could play a role in determining the course and outcome. Methods We studied in the early phase of pandemic consecutive patients (N=383) with SARS-CoV-2 infection, whose subsequent clinical course was classified as mild or severe, the latter being characterised by admission to intensive therapy unit or death. Five host gene polymorphisms (MERTK rs4374383, PNPLA3 rs738409, TLL-1 rs17047200, IFNL3 rs1297860, and INFL4 rs368234815) were assessed by using whole nucleic acids extracted from nasopharyngeal swabs. Specific protease cleavage sites of TLL-1 on the SARS-CoV-2 Spyke protein were predicted in silico. Results Male subjects and older patients were significantly at higher risk for a severe outcome (p=0.02 and p<0.001, respectively). By considering patients ≤ 65 years, after adjusting for potential confounding due to sex, an increased risk of severe outcome was found in subjects with the GG genotype of PNPLA3 (adj-OR: 4.69; 95% CI= 1.01-22.04) or TT genotype of TLL-1 (adj-OR=9.1; 95% CI= 1.45-57.3). In silico evaluation showed that TLL-1 is potentially involved in the Spike protein cleavage.Discussion Subjects carrying a GG genotype in PNPLA3 gene might have a constitutive upregulation of the NLRP3 inflammosome and be more prone to tissue damage when infected by SARS-CoV-2. The TT genotype in TLL-1 gene might affect its protease activity on the SARS-CoV-2 Spyke protein, enhancing the ability to infect or re-infect host’s cells. The untoward effect of these variants on disease course is evident in younger patients due to the relative absence of comorbidities as determinants of prognosis.

scholarly journals New α-Hydrazinophosphonic acid: Synthesis, characterization, DFT study and in silico prediction of its potential inhibition of SARS-CoV-2 main protease

2021 ◽  
Vol 1239 ◽  
pp. 130480
Author(s):  
Khalissa Benbouguerra ◽  
Nadjib Chafai ◽  
Salah Chafaa ◽  
Youcef Islam Touahria ◽  
Hamida Tlidjane
Keyword(s):  
In Silico ◽  
Acid Synthesis ◽  
Dft Study ◽  
In Silico Prediction ◽  
Main Protease

scholarly journals A novel HIV vaccine targeting the protease cleavage sites

2017 ◽  
Vol 14 (1) ◽  
Author(s):  
Hongzhao Li ◽  
Robert W. Omange ◽  
Francis A. Plummer ◽  
Ma Luo
Keyword(s):  
Hiv Vaccine ◽  
Cleavage Sites ◽  
Protease Cleavage ◽  
Protease Cleavage Sites

scholarly journals Proteolytic Cleavage of Bovine Adenovirus 3-Encoded pVIII

2017 ◽  
Vol 91 (10) ◽  
Author(s):  
Amit Gaba ◽  
Lisanework Ayalew ◽  
Niraj Makadiya ◽  
Suresh Tikoo
Keyword(s):  
Cleavage Site ◽  
Virus Assembly ◽  
Proteolytic Cleavage ◽  
Efficient Production ◽  
Cleavage Sites ◽  
Bovine Adenovirus ◽  
Protease Cleavage Site ◽  
Protease Cleavage ◽  
Protease Cleavage Sites ◽  
Single Protease

ABSTRACT Proteolytic maturation involving cleavage of one nonstructural and six structural precursor proteins including pVIII by adenovirus protease is an important aspect of the adenovirus life cycle. The pVIII encoded by bovine adenovirus 3 (BAdV-3) is a protein of 216 amino acids and contains two potential protease cleavage sites. Here, we report that BAdV-3 pVIII is cleaved by adenovirus protease at both potential consensus protease cleavage sites. Usage of at least one cleavage site appears essential for the production of progeny BAdV-3 virions as glycine-to-alanine mutation of both protease cleavage sites appears lethal for the production of progeny virions. However, mutation of a single protease cleavage site of BAdV-3 pVIII significantly affects the efficient production of infectious progeny virions. Further analysis revealed no significant defect in endosome escape, genome replication, capsid formation, and virus assembly. Interestingly, cleavage of pVIII at both potential cleavage sites appears essential for the production of stable BAdV-3 virions as BAdV-3 expressing pVIII containing a glycine-to-alanine mutation of either of the potential cleavage sites is thermolabile, and this mutation leads to the production of noninfectious virions. IMPORTANCE Here, we demonstrated that the BAdV-3 adenovirus protease cleaves BAdV-3 pVIII at both potential protease cleavage sites. Although cleavage of pVIII at one of the two adenoviral protease cleavage sites is required for the production of progeny virions, the mutation of a single cleavage site of pVIII affects the efficient production of infectious progeny virions. Further analysis indicated that the mutation of a single protease cleavage site (glycine to alanine) of pVIII produces thermolabile virions, which leads to the production of noninfectious virions with disrupted capsids. We thus provide evidence about the requirement of proteolytic cleavage of pVIII for production of infectious progeny virions. We feel that our study has significantly advanced the understanding of the requirement of adenovirus protease cleavage of pVIII.

scholarly journals Identification of the protease cleavage sites in a reconstituted Gag polyprotein of an HERV-K(HML-2) element

Retrovirology ◽  
2011 ◽  
Vol 8 (1) ◽  
pp. 30 ◽  
Author(s):  
Maja George ◽  
Torsten Schwecke ◽  
Nadine Beimforde ◽  
Oliver Hohn ◽  
Claudia Chudak ◽  
...  
Keyword(s):  
Cleavage Sites ◽  
Gag Polyprotein ◽  
Protease Cleavage ◽  
Protease Cleavage Sites

scholarly journals Regulating ENaC’s gate

2020 ◽  
Vol 318 (1) ◽  
pp. C150-C162 ◽  
Author(s):  
Thomas R. Kleyman ◽  
Douglas C. Eaton
Keyword(s):  
Cleavage Sites ◽  
Open Probability ◽  
Protease Cleavage ◽  
Inositol Phospholipids ◽  
Human Disorders ◽  
Protease Cleavage Sites ◽  
Specific Factors ◽  
The Impact ◽  
Channel Transition ◽  
Extracellular Environment

Epithelial Na+ channels (ENaCs) are members of a family of cation channels that function as sensors of the extracellular environment. ENaCs are activated by specific proteases in the biosynthetic pathway and at the cell surface and remove embedded inhibitory tracts, which allows channels to transition to higher open-probability states. Resolved structures of ENaC and an acid-sensing ion channel revealed highly organized extracellular regions. Within the periphery of ENaC subunits are unique domains formed by antiparallel β-strands containing the inhibitory tracts and protease cleavage sites. ENaCs are inhibited by Na+ binding to specific extracellular site(s), which promotes channel transition to a lower open-probability state. Specific inositol phospholipids and channel modification by Cys-palmitoylation enhance channel open probability. How these regulatory factors interact in a concerted manner to influence channel open probability is an important question that has not been resolved. These various factors are reviewed, and the impact of specific factors on human disorders is discussed.

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