OVERALL ASSESSMENT:
STRENGTHS: Overall, we conclude that this is a scientifically sound and
well-written article by Letko and Munster. The authors’ conclusions are
generally well-supported by the data. The authors report a screen that
is rapid, effective, and cost-efficient compared to previous methods to
screen coronavirus receptor usage. The authors were also the first to
show that SARS-CoV-2 uses the ACE2 receptor similar to SARS. This
demonstrates the effectiveness and rapidity of their screen. The authors
confirmed results from previous studies that protease treatment aids
viral entry but is not sufficient to promote viral entry into cells that
lack cognate receptors. Overall this a strong manuscript that provides
important information relevant to the current SARS-CoV-2 outbreak.
WEAKNESSES: Some improvements could be made to strengthen the manuscript
and provide better support for the authors’ conclusions. This study
relies heavily on a well-controlled luciferase reporter assay; the use
of another well-established virus-receptor binding assay would
strengthen the dataset surrounding the successful binding of synthesized
RBDs and their receptors. No statistical tests were applied to the
luciferase reporter data, and the replicates appear to be technical
replicates only. Pursuing multiple biological replicates and performing
appropriate statistical analysis would strengthen the authors’ claims.
Finally, the Methods require further exposition to allow these
experiments to be replicated by others, in particular concerning the
luciferase assays, protease treatments, and infections (MOI and
titering) (see specific comments below). Further development of the
methods is critical to describe this important advance in the field.
DETAILED U.P. ASSESSMENT: