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2020 ; 85
(ä): 104474
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Decoding the proteome of severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) for cell-penetrating peptides involved in pathogenesis or applicable
as drug delivery vectors
#MMPMID32712315
Hemmati S
; Behzadipour Y
; Haddad M
Infect Genet Evol
2020[Nov]; 85
(ä): 104474
PMID32712315
show ga
Synthetic or natural derived cell-penetrating peptides (CPPs) are vastly
investigated as tools for the intracellular delivery of membrane-impermeable
molecules. As viruses are intracellular obligate parasites, viral originated CPPs
have been considered as suitable intracellular shuttling vectors for cargo
transportation. A total of 310 CPPs were identified in the proteome of severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Screening the proteome of
the cause of COVID-19 reveals that SARS-CoV-2 CPPs (SCV2-CPPs) span the regions
involved in replication, protein-nucleotide and protein-protein interaction,
protein-metal ion interaction, and stabilization of homo/hetero-oligomers.
However, to find the most appropriate peptides as drug delivery vectors, one
might face several hurdles. Computational analyses showed that 94.3% of the
identified SCV2-CPPs are non-toxins, and 38% are neither antigenic nor
allergenic. Interestingly, 36.70% of SCV2-CPPs were resistant to all four groups
of protease families. Nearly 1/3 of SCV2-CPPs had sufficient inherent or induced
helix and sheet conformation leading to increased uptake efficiency. Heliquest
lipid-binding discrimination factor revealed that 44.30% of the helical SCV2-CPPs
are lipid-binding helices. Although Cys-rich derived CPPs of helicase (NSP13) can
potentially fold into a cyclic conformation in endosomes with a higher rate of
endosomal release, the most optimal SCV2-CPP candidates as vectors for drug
delivery were SCV2-CPP118, SCV2-CPP119, SCV2-CPP122, and SCV2-CPP129 of NSP12
(RdRp). Ten experimentally validated viral-derived CPPs were also used as the
positive control to check the scalability and reliability of our protocol in
SCV2-CPP retrieval. Some peptides with a cell-penetration ability known as
bioactive peptides are adopted as biotherapeutics themselves. Therefore, 59.60%,
29.63%, and 32.32% of SCV2-CPPs were identified as potential antibacterial,
antiviral, and antifungals, respectively. While 63.64% of SCV2-CPPs had
immuno-modulatory properties, 21.89% were recognized as anti-cancers.
Conclusively, the workflow of this study provides a platform for profound
screening of viral proteomes as a rich source of biotherapeutics or drug delivery
carriers.
|Antiviral Agents/pharmacology/therapeutic use
[MESH]