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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Viral Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1501200
This article is part of the Research Topic Exploring Antiviral Immune Responses and Therapeutic Strategies Against Human Coronaviruses View all 3 articles

Single spike mutation differentiating XBB.1 and XBB.1.5 enhances SARS-CoV-2 cell-to-cell transmission and facilitates serum-mediated enhancement

Provisionally accepted
Elena Criscuolo Elena Criscuolo 1Benedetta Giuliani Benedetta Giuliani 1Matteo Castelli Matteo Castelli 1Mattia Cavallaro Mattia Cavallaro 1Sofia Sisti Sofia Sisti 1Roberto Burioni Roberto Burioni 1Davide Ferrari Davide Ferrari 2Nicasio Mancini Nicasio Mancini 3Locatelli Massimo Locatelli Massimo 4Nicola Clementi Nicola Clementi 1,4*
  • 1 Vita-Salute San Raffaele University, Milan, Italy
  • 2 University of Parma, Parma, Emilia-Romagna, Italy
  • 3 Circolo Hospital and Macchi Foundation, Varese, Italy
  • 4 San Raffaele Scientific Institute (IRCCS), Milan, Lombardy, Italy

The final, formatted version of the article will be published soon.

    The constant emergence of new SARS-CoV-2 variants presents challenges for existing therapeutics. The spike glycoprotein plays a crucial role not only in the initial viral entry but also in the transmission of SARS-CoV-2 components through syncytia formation. Spike-mediated cell-to-cell transmission exhibits strong resistance to extracellular therapeutic and convalescent antibodies via a mechanism that remains elusive. In this study, we focused on two specific clinical isolates outlining how a single amino acid substitution can impact on entry kinetics and syncytia formation. This not only affects the neutralizing capacity of the sera but, most importantly, influences the ability to induce cell-cell fusion. Thus, these findings underscore the importance of thoroughly understanding the mechanism underlying S cell-cell fusion activity. Such insights will lay the groundwork for future research aimed at identifying potentially superior therapies compared to current options and improving the ability to predict the impact of forthcoming SARS-CoV-2 variants more accurately.

    Keywords: SARS-CoV-2, Spike, COVID-19, XBB.1, XBB.1.5, neutralizing antibodies, Fusion

    Received: 24 Sep 2024; Accepted: 06 Nov 2024.

    Copyright: © 2024 Criscuolo, Giuliani, Castelli, Cavallaro, Sisti, Burioni, Ferrari, Mancini, Massimo and Clementi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Nicola Clementi, Vita-Salute San Raffaele University, Milan, Italy

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.