Adaptive Evolution of Peptide Inhibitors for Mutating SARS-CoV-2.
ChemRxiv
; 2020 Jul 10.
Article
in English
| MEDLINE | ID: covidwho-1027423
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
The SARS-CoV-2 virus is currently causing a worldwide pandemic with dramatic societal consequences for the humankind. In the last decades, disease outbreaks due to such zoonotic pathogens have appeared with an accelerated rate, which calls for an urgent development ofadaptive (smart) therapeutics. Here, we develop a computational strategy to adaptively evolve peptides that could selectively inhibit mutating S protein receptor binding domains (RBDs) of different SARS-CoV-2 viral strains from binding to their human host receptor, angiotensin-converting enzyme 2 (ACE2). Starting from suitable peptide templates, based on selected ACE2 segments (natural RBD binder), we gradually modify the templates by random mutations, while retaining those mutations that maximize their RBD-binding free energies. In this adaptive evolution, atomistic molecular dynamics simulations of the template-RBD complexes are iteratively perturbed by the peptide mutations, which are retained under favorable Monte Carlo decisions. The computational search will provide libraries
of optimized therapeutics capable of reducing the SARS-CoV-2 infection on a global scale.
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Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Randomized controlled trials
Language:
English
Year:
2020
Document Type:
Article
Affiliation country:
Chemrxiv.12622667.v2
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