Optimization of VE607 to generate analogs with improved neutralization activities against SARS-CoV-2 variants
Shilei Ding, Derek Yang, Irfan Ullah, Ling Niu, Matthew Unger, Marco A. Díaz-Salinas, Monika Chandravanshi, Fei Zhou, Guillaume Beaudoin-Bussières, Mehdi Benlarbi, William D. Tolbert, Keon-Woong Yoon, Ruixue Xu, Geneviève Laroche, Fleur Gaudette, Abraham J. Morton
TL;DR
Researchers improved a drug called VE607 to better fight new SARS-CoV-2 variants, including KP.3.1.1 and XEC, and found a promising analog that works well in mice.
Contribution
The study introduces VE607 analogs with enhanced neutralization against emerging SARS-CoV-2 variants.
Findings
VE607 analogs showed improved potency against SARS-CoV-2 variants KP.3.1.1 and XEC.
DY-III-281 reduced viral burden and delayed death in transgenic mice infected with SARS-CoV-2.
Combining DY-III-281 with a modified antibody had an additive effect in reducing disease burden in mice.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains a threat to human health, particularly among immunocompromised and elderly individuals, given their heightened vulnerability to coronavirus disease 2019 (COVID-19)-associated morbidity and mortality. Recently, omicron subvariants such as KP.3.1.1 and XEC have emerged with an enhanced ability to evade humoral immunity. The development of new strategies against these variants of concern remains an intense area of research. The small molecule VE607 is an entry inhibitor that targets the Spike glycoprotein and delays virus spread in vivo. To improve the potency of this new class of SARS-CoV-2 entry inhibitors, we generated and characterized VE607 analogs and identified candidates with enhanced activity against variants, including KP.3.1.1 and XEC. Promising analogs exhibited higher inhibitory potency than the…
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Taxonomy
TopicsSARS-CoV-2 and COVID-19 Research · vaccines and immunoinformatics approaches · Monoclonal and Polyclonal Antibodies Research