Distinctive Features of the XBB.1.5 and XBB.1.16 Spike Protein Receptor-Binding Domains and Their Roles in Conformational Changes and Angiotensin-Converting Enzyme 2 Binding.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Angiotensin-Converting Enzyme 2*/genetics ; COVID-19*; Humans ; Spike Glycoprotein, Coronavirus/genetics ; SARS-CoV-2/genetics

The emergence and the high transmissibility of the XBB.1.5 and XBB.1.16 subvariants of the SARS-CoV-2 omicron has reignited concerns over the potential impact on vaccine efficacy for these and future variants. We investigated the roles of the XBB.1.5 and XBB.1.16 mutations on the structure of the spike protein's receptor-binding domain (RBD) and its interactions with the host cell receptor ACE2. To bind to ACE2, the RBD must transition from the closed-form to the open-form configuration. We found that the XBB variants have less stable closed-form structures that may make the transition to the open-form easier. We found that the mutations enhance the RBD-ACE2 interactions in XBB.1.16 compared to XBB.1.5. We observed significant structural changes in the loop and motif regions of the RBD, altering well-known antibody-binding sites and potentially rendering primary RBD-specific antibodies ineffective. Our findings elucidate how subtle structural changes and interactions contribute to the subvariants' fitness over their predecessors.

Biochem Biophys Res Commun. 2021 Oct 15;574:14-19. (PMID: 34425281)
Cell. 2022 Jul 7;185(14):2422-2433.e13. (PMID: 35772405)
Nature. 2023 Jan;613(7943):222-223. (PMID: 36624320)
J Mol Graph. 1996 Feb;14(1):33-8, 27-8. (PMID: 8744570)
J Phys Chem B. 2021 Jul 8;125(26):7101-7107. (PMID: 34110159)
Nature. 2003 Nov 27;426(6965):450-4. (PMID: 14647384)
Nat Commun. 2020 Sep 11;11(1):4541. (PMID: 32917884)
Nat Med. 2022 Sep;28(9):1785-1790. (PMID: 35760080)
Nat Commun. 2022 Aug 24;13(1):4958. (PMID: 36002453)
Mol Ther Nucleic Acids. 2023 Jun 13;32:61-63. (PMID: 36938362)
Sci Immunol. 2020 Oct 8;5(52):. (PMID: 33033172)
Nat Chem. 2021 Oct;13(10):963-968. (PMID: 34413500)
Nat Methods. 2017 Jan;14(1):71-73. (PMID: 27819658)
Nature. 2021 May;593(7857):130-135. (PMID: 33684923)
Sci Immunol. 2020 Jun 11;5(48):. (PMID: 32527802)
Cell. 2021 Apr 29;184(9):2362-2371.e9. (PMID: 33735608)
J Chem Theory Comput. 2016 Jan 12;12(1):405-13. (PMID: 26631602)
J Mol Model. 2023 Mar 24;29(4):109. (PMID: 36964244)
BMJ. 2021 Feb 5;372:n359. (PMID: 33547053)
J Chem Phys. 2020 Jul 28;153(4):044130. (PMID: 32752662)
J Comput Chem. 2008 Aug;29(11):1859-65. (PMID: 18351591)
Science. 2022 Feb 18;375(6582):760-764. (PMID: 35050643)
Phys Chem Chem Phys. 2022 Apr 20;24(16):9123-9129. (PMID: 35395667)
Nature. 2023 Jan 10;:. (PMID: 36631585)
Nature. 2022 Nov;611(7935):213-214. (PMID: 36307585)
Comput Biol Med. 2022 Sep;148:105903. (PMID: 35932731)
J Med Virol. 2021 Apr;93(4):2132-2140. (PMID: 33090512)
MedComm (2020). 2023 Mar 15;4(2):e239. (PMID: 36938325)
Cell. 2020 Sep 3;182(5):1295-1310.e20. (PMID: 32841599)
Nature. 2022 Feb;602(7898):657-663. (PMID: 35016194)
Cell Res. 2021 Jul;31(7):732-741. (PMID: 34021265)
Science. 2005 Sep 16;309(5742):1864-8. (PMID: 16166518)
N Engl J Med. 2023 Mar 23;388(12):1142-1145. (PMID: 36856580)
Nat Rev Mol Cell Biol. 2022 Jan;23(1):3-20. (PMID: 34611326)

Keywords: SARS-CoV-2; XBB.1.16; XBB.1.5; computational; molecular dynamics; mutations; omicron; receptor-binding domain; spike protein; structural changes

EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
0 (spike protein, SARS-CoV-2)
0 (Spike Glycoprotein, Coronavirus)

Date Created: 20230826 Date Completed: 20230828 Latest Revision: 20230829

20230830

PMC10454900

10.3390/ijms241612586

37628766