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. 2020 Jun 9:9:576.
doi: 10.12688/f1000research.24074.1. eCollection 2020.

Potential chimeric peptides to block the SARS-CoV-2 spike receptor-binding domain

Debmalya Barh #  1 , Sandeep Tiwari #  2 , Bruno Silva Andrade  3 , Marta Giovanetti  2   4 , Eduardo Almeida Costa  5 , Ranjith Kumavath  6 , Preetam Ghosh  7 , Aristóteles Góes-Neto  8 , Luiz Carlos Junior Alcantara  2   4 , Vasco Azevedo  2
Affiliations

Potential chimeric peptides to block the SARS-CoV-2 spike receptor-binding domain

Debmalya Barh et al. F1000Res. .

Abstract

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.

Keywords: ACE2; Antiviral peptides; COVID-19; SARS-CoV-2; Spike protein; nCoV-19; peptide design.

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Conflict of interest statement

No competing interests were disclosed.

Figures

Figure 1.
Figure 1.. The binding interfaces between SARS-CoV-2 Spike receptor-binding domain with hACE2 derived peptides.
( A) AC26, ( B) AC23, and ( C) AC20.
Figure 2.
Figure 2.. The binding interfaces between SARS-CoV-2 Spike receptor-binding domain with peptides screened from the antimicrobial peptide databases.
( A) DBP1, ( B) DBP2, ( C) DBP3, ( D) DBP4, ( E) DBP5, ( F) DBP6, and ( G) DBP7.
Figure 3.
Figure 3.. The binding interfaces between SARS-CoV-2 Spike receptor-binding domain with designed chimeric peptides.
( A) cnCoVP-1, ( B) cnCoVP-2, ( C) cnCoVP-3, ( D) cnCoVP-4, ( E) cnCoVP-5, ( F) cnCoVP-6, and ( G) cnCoVP-7.
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