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Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies.
Cell Mol Life Sci. 2020 Jul 04 [Online ahead of print]CM

Abstract

The recent severe acute respiratory syndrome, known as Coronavirus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare a state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, the scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim, we performed an in silico comparative modeling analysis, which allows gaining new insights into the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor-binding domain (RBD), along interactions with human cells angiotensin-converting enzyme 2 (ACE2) receptor, that favor human cell invasion. Furthermore, our analysis provides (1) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, aiming to prevent interactions with the human ACE2, and (2) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high-affinity antibodies against present and future coronaviruses able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD-ACE2 interactions for the development of new vaccines, diagnostic kits, and other treatments based on the targeting of SARS-CoV-2 spike protein.

Authors+Show Affiliations

Laboratory of Biochemistry, Molecular and Structural Biology, Department of Biosciences, Biotechnologies, Biopharmaceutics, University of Bari, Via E. Orabona, 4, 70125, Bari, Italy.Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Via Amendola 165/A, 70126, Bari, Italy.Laboratory of Biochemistry, Molecular and Structural Biology, Department of Biosciences, Biotechnologies, Biopharmaceutics, University of Bari, Via E. Orabona, 4, 70125, Bari, Italy.Laboratory of Biochemistry, Molecular and Structural Biology, Department of Biosciences, Biotechnologies, Biopharmaceutics, University of Bari, Via E. Orabona, 4, 70125, Bari, Italy. BROWSer S.r.l. (https://browser-bioinf.com/) c/o Department of Biosciences, Biotechnologies, Biopharmaceutics, University "Aldo Moro" of Bari, Via E. Orabona, 4, 70126, Bari, Italy.Laboratory of Biochemistry, Molecular and Structural Biology, Department of Biosciences, Biotechnologies, Biopharmaceutics, University of Bari, Via E. Orabona, 4, 70125, Bari, Italy. ciro.pierri@uniba.it. BROWSer S.r.l. (https://browser-bioinf.com/) c/o Department of Biosciences, Biotechnologies, Biopharmaceutics, University "Aldo Moro" of Bari, Via E. Orabona, 4, 70126, Bari, Italy. ciro.pierri@uniba.it.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32623480

Citation

Mercurio, Ivan, et al. "Protein Structure Analysis of the Interactions Between SARS-CoV-2 Spike Protein and the Human ACE2 Receptor: From Conformational Changes to Novel Neutralizing Antibodies." Cellular and Molecular Life Sciences : CMLS, 2020.
Mercurio I, Tragni V, Busto F, et al. Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies. Cell Mol Life Sci. 2020.
Mercurio, I., Tragni, V., Busto, F., De Grassi, A., & Pierri, C. L. (2020). Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies. Cellular and Molecular Life Sciences : CMLS. https://doi.org/10.1007/s00018-020-03580-1
Mercurio I, et al. Protein Structure Analysis of the Interactions Between SARS-CoV-2 Spike Protein and the Human ACE2 Receptor: From Conformational Changes to Novel Neutralizing Antibodies. Cell Mol Life Sci. 2020 Jul 4; PubMed PMID: 32623480.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies. AU - Mercurio,Ivan, AU - Tragni,Vincenzo, AU - Busto,Francesco, AU - De Grassi,Anna, AU - Pierri,Ciro Leonardo, Y1 - 2020/07/04/ PY - 2020/04/16/received PY - 2020/06/22/accepted PY - 2020/06/10/revised PY - 2020/7/6/entrez PY - 2020/7/6/pubmed PY - 2020/7/6/medline KW - ACE2 and ACE inhibitors KW - COVID-19 KW - Comparative modeling KW - Coronavirus KW - Fold recognition tools KW - Neutralizing antibodies KW - Receptor binding domain KW - SARS-CoV-2 KW - Spike KW - Spike post-fusion conformation KW - n-CoV19 JF - Cellular and molecular life sciences : CMLS JO - Cell. Mol. Life Sci. N2 - The recent severe acute respiratory syndrome, known as Coronavirus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare a state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, the scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim, we performed an in silico comparative modeling analysis, which allows gaining new insights into the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor-binding domain (RBD), along interactions with human cells angiotensin-converting enzyme 2 (ACE2) receptor, that favor human cell invasion. Furthermore, our analysis provides (1) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, aiming to prevent interactions with the human ACE2, and (2) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high-affinity antibodies against present and future coronaviruses able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD-ACE2 interactions for the development of new vaccines, diagnostic kits, and other treatments based on the targeting of SARS-CoV-2 spike protein. SN - 1420-9071 UR - https://www.unboundmedicine.com/medline/citation/32623480/Protein_structure_analysis_of_the_interactions_between_SARS-CoV-2_spike_protein_and_the_human_ACE2_receptor:_from_conformational_changes_to_novel_neutralizing_antibodies L2 - https://doi.org/10.1007/s00018-020-03580-1 DB - PRIME DP - Unbound Medicine ER -
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