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: