Samantha L. Wakerlin
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Samantha L. Wakerlin has a total of 4 co-authors. Here are the top co-authors by number of shared publications:
- Andrew J. Lindsay
School of Biochemistry and Cell Biology, University College Cork, Cork T12 XF62, Ireland
1 shared publication - Caroline Coleman-Vaughan
Department of Biological Sciences, Munster Technological University, Bishopstown, Cork, Ireland
1 shared publication - James V. Harte
EOLAS Research Group, Cork University Hospital, Wilton, T12 DC4A Cork, Ireland
1 shared publication - Justin V. McCarthy
Signal Transduction Laboratory, Biochemistry Department, University College Cork, Cork, Ireland
1 shared publication
Latest Publications
- Open Access
Metalloprotease-Dependent S2′-Activation Promotes Cell–Cell Fusion and Syncytiation of SARS-CoV-2
SARS-CoV-2 cell–cell fusion and syncytiation is an emerging pathomechanism in COVID-19, but the precise factors contributing to the process remain ill-defined. In this study, we show that metalloproteases promote SARS-CoV-2 spike protein-induced syncytiation in the absence of established serine proteases using in vitro cell–cell fusion assays. We also show that metalloproteases promote S2′-activation of the SARS-CoV-2 spike protein, and that metalloprotease inhibition significantly reduces the syncytiation of SARS-CoV-2 variants of concern. In the presence of serine proteases, however, metalloprotease inhibition does not reduce spike protein-induced syncytiation and a combination of metalloprotease and serine protease inhibition is necessitated. Moreover, we show that the spike protein induces metalloprotease-dependent ectodomain shedding of the ACE2 receptor and that ACE2 shedding contributes to spike protein-induced syncytiation. These observations suggest a benefit to the incorporation of pharmacological inhibitors of metalloproteases into treatment strategies for patients with COVID-19.
Open AccessMetalloprotease-Dependent S2′-Activation Promotes Cell–Cell Fusion and Syncytiation of SARS-CoV-2
SARS-CoV-2 cell–cell fusion and syncytiation is an emerging pathomechanism in COVID-19, but the precise factors contributing to the process remain ill-defined. In this study, we show that metalloproteases promote SARS-CoV-2 spike protein-induced syncytiation in the absence of established serine proteases using in vitro cell–cell fusion assays. We also show that metalloproteases promote S2′-activation of the SARS-CoV-2 spike protein, and that metalloprotease inhibition significantly reduces the syncytiation of SARS-CoV-2 variants of concern. In the presence of serine proteases, however, metalloprotease inhibition does not reduce spike protein-induced syncytiation and a combination of metalloprotease and serine protease inhibition is necessitated. Moreover, we show that the spike protein induces metalloprotease-dependent ectodomain shedding of the ACE2 receptor and that ACE2 shedding contributes to spike protein-induced syncytiation. These observations suggest a benefit to the incorporation of pharmacological inhibitors of metalloproteases into treatment strategies for patients with COVID-19.