The Veesler Lab

Arabian MERS-CoV Spikes Evade Soluble DPP4 Inhibition MERS-CoV often causes severe disease but spreads poorly between humans. If it adapts for efficient transmission, pandemic risk rises - especially since immunity from SARS-CoV-2 or seasonal coronaviruses likely offers little protection. The virus infects dromedary camels (mild disease) and spills over to humans. It circulates in African & Arabian camels, yet human cases are almost exclusively linked to Arabian strains - why remains incompletely understood. We compared African vs Arabian spikes using a safe pseudovirus system. Result: no major differences in DPP4 binding, entry into human cells, protease usage, antibody neutralization, or heat stability. But: Soluble DPP4 inhibited entry differently. Arabian spikes were less inhibited than African ones - due to mutation Q1020R. What is soluble DPP4? DPP4 exists in membrane-bound (entry receptor) and soluble forms. At high levels (lab conditions), soluble DPP4 was found to inhibit infection. Our data suggest soluble DPP4 naturally present in human plasma may moderately restrict MERS-CoV entry, and Q1020R helps evade this effect. This could matter since virus is detected in the blood in severe cases. Bottom line: soluble DPP4 may be a natural barrier - one that Arabian MERS-CoV strains may overcome more efficiently than African strains. Great work by @Ah970215 and Markus Hoffmann & collaborators Our paper: Chen et al, Journal of Virology, 2026 Q1020R in the spike proteins of MERS-CoV from Arabian camels confers resistance against soluble human DPP4 | Journal of Virology journals.asm.org/doi/10.1128/jv…

Excited to share our paper in @NatureSMB with @antoinekoehl Hypervariable loop profiling decodes sequence determinants of antibody stability nature.com/articles/s4159… The main question: how do antibody CDRs create enormous binding diversity without breaking folding?

We are grateful for the participation of Courtney Yoshiyama, @YoungjunPark11 @dabiophysicist Jack Brown & our amazing collaborators in the @tylernstarr lab @Vir_Biotech 12/12

Using #cryoEM and functional assays, we showed that MB11 binds to the PDCoV RBD as designed and inhibits viral entry by preventing engagement of the host receptor through steric hindrance, explaining its potent neutralizing activity 11/12

Can we use #proteindesign to develop countermeasures before viruses cause pandemics? We computationally designed an ultrapotent and broadly neutralizing deltacoronavirus miniprotein. Led by Nathan Avery @hhmi_science 1/12 pnas.org/doi/10.1073/pn…

Must read

New online! TMPRSS2-mediated coronavirus spike activation and inhibition dlvr.it/TSGjRx

@dabiophysicist @StuartTurville Link to the paper 20/19 nature.com/articles/s4159…

We are incredibly grateful to everyone involved including Jimin Lee, Cecily Gibson, Cameron Stewart, Ale Tortorici @dabiophysicist & our wonderful collaborators Lisa Purcell @StuartTurville Nick Riley Federica Sallusto Jun Siong Low ... 19/19

How are host proteases promoting coronavirus entry into cells? Find out by reading our latest manuscript led by Matt McCallum Brett Case Jack Brown @YoungjunPark11 in collaboration with @msdiamondlab 1/19