Barh, D.; Tiwari, S.; Silva Andrade, B.; Giovanetti, M.; Kumavath, R.; Ghosh, P.; Góes-Neto, A.; Carlos Junior Alcantara, L.; Azevedo, V. Potential Chimeric Peptides to Block the SARS-CoV-2 Spike RBD. Preprints2020, 2020040347. https://doi.org/10.20944/preprints202004.0347.v1
Barh, D., Tiwari, S., Silva Andrade, B., Giovanetti, M., Kumavath, R., Ghosh, P., Góes-Neto, A., Carlos Junior Alcantara, L., & Azevedo, V. (2020). Potential Chimeric Peptides to Block the SARS-CoV-2 Spike RBD. Preprints. https://doi.org/10.20944/preprints202004.0347.v1
Barh, D., Luiz Carlos Junior Alcantara and Vasco Azevedo. 2020 "Potential Chimeric Peptides to Block the SARS-CoV-2 Spike RBD" Preprints. https://doi.org/10.20944/preprints202004.0347.v1
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 RBD (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 (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 interacting 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. Conclusion: All the ten peptides need experimental validation for their therapeutic efficacy.
antiviral peptides; COVID-19; SARS-CoV-2; nCoV-19; peptide design; ACE2; Spike protein
Biology and Life Sciences, Virology
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