ArticleJournal of virology2020
Trypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus Infection.
Article in Journal of virology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
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Who cites it
135 citing papers in PubMed, 226 citations in OpenAlex.
- Exploring coronavirus cell entry with functional viromics.Journal of virology · 2026Review
- Discovery of EGT710, an Oral Nonpeptidomimetic Reversible Covalent SARS-CoV-2 Main Protease Inhibitor.Journal of medicinal chemistry · 2026Article
- Immunogenicity and protective efficacy of MERS CoV, NL140422, and HKU4 spike protein nanoparticle vaccines.Npj viruses · 2026Article
- Effect of the S2' site cleavage on SARS-CoV-2 spike.Nature communications · 2025Article
- Structural and phenotypic plasticity of the RBD loop2 region is a key determinant for HKU5r-CoVs' emergence in mink.bioRxiv : the preprint server for biology · 2025Article
- Bat sarbecovirus WIV1-CoV bears an adaptive mutation that alters spike dynamics and enhances ACE2 binding.PLoS pathogens · 2025Article
- Expression of spike and hemagglutinin-esterase proteins is necessary to recover infectious recombinant bovine coronavirus.Journal of virology · 2025Article
- Infection of animal coronaviruses into a bat cell line from the kidney of Pipistrellus abramus.The Journal of veterinary medical science · 2025Article
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- Structural determinants of rotavirus proteolytic activation.PLoS pathogens · 2025Article
- Merbecovirus S2 subunit vaccines elicit cross reactive antibodies and provide partial protection against MERS coronavirus.Npj viruses · 2025Article
- HKU5 bat merbecoviruses engage bat and mink ACE2 as entry receptors.Nature communications · 2025Article
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- Designed miniproteins potently inhibit and protect against MERS-CoV.Cell reports · 2025Article
- ACE2 from Pipistrellus abramus bats is a receptor for HKU5 coronaviruses.Nature communications · 2025Article
- Nonviral protein cages as tools to decipher and combat viral threats.Npj viruses · 2025Review
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- Molecular basis of convergent evolution of ACE2 receptor utilization among HKU5 coronaviruses.Cell · 2025Article
- Receptor-binding proteins from animal viruses are broadly compatible with human cell entry factors.Nature microbiology · 2025Article
- Article
75 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Traditionally, the emergence of coronaviruses (CoVs) has been attributed to a gain in receptor binding in a new host. Our previous work with severe acute respiratory syndrome (SARS)-like viruses argued that bats already harbor CoVs with the ability to infect humans without adaptation. These results suggested that additional barriers limit the emergence of zoonotic CoV. In this work, we describe overcoming host restriction of two Middle East respiratory syndrome (MERS)-like bat CoVs using exogenous protease treatment. We found that the spike protein of PDF2180-CoV, a MERS-like virus found in a Ugandan bat, could mediate infection of Vero and human cells in the presence of exogenous trypsin. We subsequently show that the bat virus spike can mediate the infection of human gut cells but is unable to infect human lung cells. Using receptor-blocking antibodies, we show that infection with the PDF2180 spike does not require MERS-CoV receptor DPP4 and antibodies developed against the MERS spike receptor-binding domain and S2 portion are ineffective in neutralizing the PDF2180 chimera. Finally, we found that the addition of exogenous trypsin also rescues HKU5-CoV, a second bat group 2c CoV. Together, these results indicate that proteolytic cleavage of the spike, not receptor binding, is the primary infection barrier for these two group 2c CoVs. Coupled with receptor binding, proteolytic activation offers a new parameter to evaluate the emergence potential of bat CoVs and offers a means to recover previously unrecoverable zoonotic CoV strains.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.