Content of review 1, reviewed on June 16, 2020

In this article, the authors study the differences in West African viruses may be relevant to zoonotic potential, and tried to fill in the gap of knowledge on the genetic information from MERS-CoV in Africa. Interestingly they found that MERS-CoV circulating in dromedaries in Africa are phylogenetically distinct from viruses in the Arabian Peninsula. It is an article of great importance and it opens new doors for novel research. My main comment on this manuscript is that the authors could have elaborated more on the great importance of this work, relevance of their findings and contextualize better with literature on the MERS-CoV, the methodology chosen and the relationship between them. Thus, I only have small comments/suggestions, mainly on the structure of the manuscript.

  1. Title and Abstract In general, I think the article is of great importance in its field. The title is captivating and it is an accurate representation of the manuscript. The references are also current to date and relevant to the field. The abstract matches the article and the aim is stated.

In my opinion, only the methodology within the abstract is very succinct. Although, in general, abstracts have limited number of words, the authors only state “genetically and phenotypically characterized MERS- CoV”, and it would be helpful to add few more keywords on which methodology was used in this work to captivate the reader and reveal a little bit more information.

  1. Introduction The introduction is very clear and concise, but maybe too small. In this case, PNAS does not impose a limited low number of words on the introduction section nor references. The problem is not exactly the size, but the content that might be missing where I believe it could improve if extended. In my opinion, for example, I think the introduction should address and include a better overview on the background and existing literature on coronaviruses and more specifically MERS-CoV, as well as why did the authors used the methodology chosen. Like this, it would be better to understand the gap in research and why filling this knowledge gap is important.

This connects me to another point of the introduction which is that, in my opinion, the aim and importance of this study are not very clearly stated. I would suggest not only a more thorough literature research, but trying to explain why this work is so important for the community or the real-world benefits of it. Nevertheless, this work is very necessary given what is already known about the topic, it just needs to state this in a clearer way like it is on the last sentence of the “Significance”.

Moreover, similar to what I mentioned in the abstract, there is no clear statement of methods used to achieve the goal. As a reader, after scanning the abstract and introduction, it is still not possible to understand which methods/techniques were used, unless the reader checks directly the methods or results sections. I would also suggest that the authors could revise their introduction in order to try and create flow between sentences.

  1. Methods and data The methods part is very detailed and complete (including supporting information). Only here is possible to start understanding which methods were actually used within this work. Selected sampling meets the research integrity expected. It is representative and includes cross-countries sampling. Safety practices are adequate and all procedures can be generalized, comparable and replicated. The methodology chosen is, in general, well applied and appropriated. However, personally I cannot judge on “Experimental Infection of Mice” as it is not within my field of research. Nevertheless, ethically, the authors state that all animal studies were approved by the Institutional Animal Care and Utilization Committee at the University of Iowa.

The data is presented in a proper way. All figures and table S1 are relevant and clearly presented and their labeling is appropriate. Results are presented clearly, directly and in a very detailed way, and there is focus and purpose throughout the text. Also, underlying assumptions are fulfilled.

Just some comments on the methods. The MERS-CoV full genomes were phylogenetically analysed using PhyML and BEAST with HKY+Γ and GTR models respectively which is fine. But the authors did not state why or how did they choose these specific models (e.g. if it was the best-fit model as determined by jModelTest or from any other software, or if they just chose these models for some other reason). One has to choose the best-fit model to the data, and when not chosen appropriately, it might influence results.

Also, some important abbreviations for text comprehension have no explanation assuming all readers know what is relates to, for example, “ORF” region or “IFN” meaning (Open Reading Frame region and Interferon, respectively) - either on the main text or on the supporting information.

  1. Discussion and conclusions The authors explicitly state their findings, and the conclusions are supported by their major results. The conclusions answer the aims of the study and the authors state their limitations and suggestions for future research. In the end, there are no over-interpretations and the reader can gain knowledge with the clear conclusions.

However, in my opinion, the authors could have elaborated more on the great importance and relevance of their findings. Also, there is missing a bit more introductory information not only on ORF and IFN functions, but on what is known on the relationship between them and coronaviruses (and/or other viruses). I would suggest that the discussion could have been at the beginning a bit less descriptive and instead include first more context around the subject. This means that maybe there should have been a bit more literature description at the beginning of the discussion that would relate their work to previous findings, instead of just vaguely citing them and being very descriptive in major results. Only later, authors mention some other works and compared them with their findings, but in my opinion, it would be very important to create a context at the beginning of the discussion, as the introduction was also not very extensive and elaborated. This would be helpful to better understand their findings, not only to the scientific community but principally people that are interested outside the scientific community.

Source

    © 2020 the Reviewer.

References

    W., C. D. K., Y., H. K. P., M., P. R. A. P., Eve, M., Daniela, N., Jincun, Z., Rudragouda, C., Gytis, D., O., O. J., Amadou, T., Ouafaa, F., Abraham, A., F., D. G., Doreen, M., W., C. M. C., M., N. J., K., M. D., A., K. S., Gezahegne, M., Ziqi, Z., Y., S. R. T., G., H. M., J., W. R., Francois, R., Andrew, R., M., P. L. L., Stanley, P., Christian, D., Veronique, C., Malik, P. 2018. MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity. Proceedings of the National Academy of Sciences.