From the Wuhan-Hu-1 strain to the XD and XE variants: is targeting the SARS-CoV-2 spike protein still a pharmaceutically relevant option against COVID-19?. (31st December 2022)

• Record Type: Journal Article
• Authors: Pavan, Matteo; Bassani, Davide; Sturlese, Mattia; Moro, Stefano
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 37:Number 1(2022)
• Page Start: 1704
• Page End: 1714
• Publication Date: 2022-12-31
• Subjects: SARS-CoV-2 -- COVID-19 -- XE variant -- XD variant -- Spike protein -- Mpro -- Paxlovid; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2022.2081847
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: Since the outbreak of the COVID-19 pandemic in December 2019, the SARS-CoV-2 genome has undergone several mutations. The emergence of such variants has resulted in multiple pandemic waves, contributing to sustaining to date the number of infections, hospitalisations, and deaths despite the swift development of vaccines, since most of these mutations are concentrated on the Spike protein, a viral surface glycoprotein that is the main target for most vaccines. A milestone in the fight against the COVID-19 pandemic has been represented by the development of Paxlovid, the first orally available drug against COVID-19, which acts on the Main Protease (Mpro). In this article, we analyse the structural features of both the Spike protein and the Mpro of the recently reported SARS-CoV-2 variant XE, as well the closely related XD and XF ones, discussing their impact on the efficacy of existing treatments against COVID-19 and on the development of future ones.