ABSTRACT
Background and Objectives: * The spike (S) protein of SARS-CoV-2 virus binds to the host cell receptor which facilitates the virus entry. This interaction is primed by host cell proteases like furin and TMPRSS2 acting at S1/S2 and S2' cleavage sites, respectively. * Both the cleavage sites have Serine and Proline residues conversed in all the coronaviruses. It has been speculated that mutations at these conserved residues may provide a gain-offunction, easing the SARS-CoV-2 entry into the host cell and cellto- cell spread, thus modulating the virulence and pathogenicity. * Unravelling the effects of these conserved residues in the S protein cleavage site in virus entry and transmission might facilitate development of novel therapeutics. Material(s) and Method(s): * This study employed a lentivirus based pseudovirus (PSV) system, where P and S residues at S1/S2 site of Spike gene, present in an expression vector, were mutated to Alanine (Fig A). * We then assessed the expression of the SARS-CoV-2-S variants in HEK293T cells and tested the infectivity and fusogenicity of mutant PSV and spike, respectively in the presence or absence of S1/S2 and S2' protease inhibitors. Results and Conclusion(s): * Conserved Serine residue mutation (S2SA) at S2' cleavage site resulted in complete loss of spike cleavage by furin and cathepsins (Fig B). * TMPRSS2 protease treatment was not able to rescue loss of spike cleavage and fusogenicity (Fig C & D). * S2SA mutant showed no significant response against E-64d and TMPRSS2 inhibitor. * Serine at S2' site in spike protein provides an ideal site to be further evaluated for the therapeutic purpose against SARS-CoV- 2.
ABSTRACT
Objective: The effect of Coronavirus disease 2019 (COVID-19) pandemic on performance of neuro-endovascular procedures has not been quantified. Background: The effect of Coronavirus disease 2019 (COVID-19) pandemic on performance of neuro-endovascular procedures has not been quantified. Design/Methods: We performed an audit of performance of neuro-endovascular procedures at 18 institutions (7 countries) for two periods;January to April 2019 and 2020, to identify changes in various core procedures. We divided the region where the hospital was located based on the median value of total number of COVID-19 cases per 100,00 population-into high and low prevalent regions Results: Between 2019 and 2020, there was a reduction in number of cerebral angiograms (30.9% reduction), mechanical thrombectomy (8% reduction), carotid artery stent placement for symptomatic (22.7% reduction) and asymptomatic (43.4% reduction) stenoses, intracranial angioplasty and/or stent placement (45% reduction), and endovascular treatment of unruptured intracranial aneurysms (44.6% reduction) and ruptured (22.9% reduction) and unruptured brain arteriovenous malformations (66.4% reduction). There was an increase in treatment of ruptured intracranial aneurysms (10% increase) and other neuro-endovascular procedures (34.9% increase). There was no relationship between procedural volume change and intuitional location in high or low COVID-19 prevalent regions. The procedural volume reduction was mainly observed in March-April 2020. Conclusions: We provided an international multicenter view of changes in neuro-endovascular practices to better understand the gaps in provision of care and identify individual procedures which are susceptible to change.