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

Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur, WB, India. Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. Laboratório de Bioinformática e Química Computacional, Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia (UESB), Jequié, Bahia, Brazil. Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. Núcleo de Biologia Computacional e Gestão de Informações Biotecnológicas (NBCGIB), Universidade Estadual de Santa Cruz (UESC), Km 16, Salobrinho, Ilhéus, Bahia, CEP 45662-900, Brazil. Department of Genomic Science, School of Biological Sciences, University of Kerala, Tejaswini Hills, Periya P.O, Kasaragod, Kerala, 671316, India. Department of Computer Science, Virginia Commonwealth University, Richmond, VA, 23284, USA. Laboratório de Biologia Molecular e Computacional de Fungos, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.

F1000Research. 2020;:576
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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.