Applications of predictive modelling early in the COVID-19 epidemic

SARS-CoV-2's origin should be investigated worldwide for pandemic prevention

COVID-19: What do we know?

Electrocardiographic features of patients with COVID-19: One year of unexpected manifestations

Treatment of Severe Acute Respiratory Syndrome

Imperfect storm: is interleukin-33 the Achilles heel of COVID-19?

Epidemiologic Changes Caused by the Preventive Measures for the Coronavirus Disease 2019 Pandemic: An Additional Challenge for Pediatricians

Multisystem Inflammatory Syndrome in Children and Kawasaki Disease: Two Different Illnesses with Overlapping Clinical Features

Testing the Asymptomatic Pre-Surgical Population for Severe Acute Respiratory Syndrome Coronavirus 2

The immunology of COVID-19: is immune modulation an option for treatment?

Structural Basis of SARS-CoV-2 Polymerase Inhibition by Favipiravir

SummaryThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike N-terminal domain (NTD) remains poorly characterized despite enrichment of mutations in this region across variants of concern (VOCs). Here, we examine the contribution of the NTD to infection and cell-cell fusion by constructing chimeric spikes bearing B.1.617 lineage (Delta and Kappa variants) NTDs and generating spike pseudotyped lentivirus. We find that the Delta NTD on a Kappa or wild-type (WT) background increases S1/S2 cleavage efficiency and virus entry, specifically in lung cells and airway organoids, through use of TMPRSS2. Delta exhibits increased cell-cell fusogenicity that could be conferred to WT and Kappa spikes by Delta NTD transfer. However, chimeras of Omicron BA.1 and BA.2 spikes with a Delta NTD do not show more efficient TMPRSS2 use or fusogenicity. We conclude that the NTD allosterically modulates S1/S2 cleavage and spike-mediated functions in a spike context-dependent manner, and allosteric interactions may be lost when combining regions from more distantly related VOCs.

Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?

SNX27-mediated endocytic recycling of GLUT1 is suppressed by SARS-CoV-2 spike, possibly explaining neuromuscular disorders in patients with COVID-19

COVID-19 vasculitis and novel vasculitis mimics.

Viruses require specific cellular receptors to infect their target cells. Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for two divergent coronaviruses, SARS coronavirus (SARS-CoV) and human coronavirus NL63 (HCoV-NL63). In addition to hostcell receptors, lysosomal cysteine proteases are required for productive infection by some viruses. Here we show that SARS-CoV, but not HCoV-NL63, utilizes the enzymatic activity of the cysteine protease cathepsin L to infect ACE2-expressing cells. Inhibitors of cathepsin L blocked infection by SARS-CoV and by a retrovirus pseudotyped with the SARS-CoV spike (S) protein but not infection by HCoV-NL63 or a retrovirus pseudotyped with the HCoV-NL63 S protein. Expression of exogenous cathepsin L substantially enhanced infection mediated by the SARS-CoV S protein and by filovirus GP proteins but not by the HCoV-NL63 S protein or the vesicular stomatitis virus G protein. Finally, an inhibitor of endosomal acidification had substantially less effect on infection mediated by the HCoV-NL63 S protein than on that mediated by the SARS-CoV S protein. Our data indicate that two coronaviruses that utilize a common receptor nonetheless enter cells through distinct mechanisms.