Potential chimeric peptides to block the SARS-CoV-2 spike receptor-binding domain
Autor: | Preetam Ghosh, Ranjith Kumavath, Marta Giovanetti, Vasco Azevedo, Sandeep Tiwari, Bruno Silva Andrade, Eduardo Almeida Costa, Luiz Carlos Junior Alcantara, Debmalya Barh, Aristóteles Góes-Neto |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Coronavirus disease 2019 (COVID-19) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Pneumonia Viral Antiviral peptides nCoV-19 ACE2 Sequence (biology) Peptide Computational biology Spike protein Peptidyl-Dipeptidase A General Biochemistry Genetics and Molecular Biology Virus Betacoronavirus 03 medical and health sciences 0302 clinical medicine Humans General Pharmacology Toxicology and Pharmaceutics Pandemics chemistry.chemical_classification General Immunology and Microbiology SARS-CoV-2 Chemistry COVID-19 Articles General Medicine Experimental validation Antibacterial peptide Amino acid peptide design 030104 developmental biology 030220 oncology & carcinogenesis Spike Glycoprotein Coronavirus Receptors Virus Angiotensin-Converting Enzyme 2 Coronavirus Infections Peptides Research Article |
Zdroj: | F1000Research |
ISSN: | 2046-1402 |
Popis: | Background:There are no known medicines or vaccines to control the COVID-19 pandemic caused by SARS-CoV-2 (nCoV). Antiviral peptides are superior to conventional drugs and may also be effective against COVID-19. Hence, we investigated the SARS-CoV-2 Spike receptor-binding domain (nCoV-RBD) that interacts with hACE2 for viral attachment and entry.Methods:Three strategies and bioinformatics approaches were employed to design potential nCoV-RBD - hACE2 interaction-blocking peptides that may restrict viral attachment and entry. Firstly, the key residues interacting with nCoV-RBD - hACE2 are identified and hACE2 sequence-based peptides are designed. Second, peptides from five antibacterial peptide databases that block nCoV-RBD are identified; finally, a chimeric peptide design approach is used to design peptides that can bind to key nCoV-RBD residues. The final peptides are selected based on their physiochemical properties, numbers and positions of key residues binding, binding energy, and antiviral properties.Results:We found that: (i) three amino acid stretches in hACE2 interact with nCoV-RBD; (ii) effective peptides must bind to three key positions of nCoV-RBD (Gly485/Phe486/Asn487, Gln493, and Gln498/Thr500/Asn501); (iii) Phe486, Gln493, and Asn501 are critical residues; (iv) AC20 and AC23 derived from hACE2 may block two key critical positions; (iv) DBP6 identified from databases can block the three sites of the nCoV-RBD and interacts with one critical position, Gln498; (v) seven chimeric peptides were considered promising, among which cnCoVP-3, cnCoVP-4, and cnCoVP-7 are the top three; and (vi) cnCoVP-4 meets all the criteria and is the best peptide.Conclusions:To conclude, using three different bioinformatics approaches, we identified 17 peptides that can potentially bind to the nCoV-RBD that interacts with hACE2. Binding these peptides to nCoV-RBD may potentially inhibit the virus to access hACE2 and thereby may prevent the infection. Out of 17, 10 peptides have promising potential and need further experimental validation. |
Databáze: | OpenAIRE |
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