Review 1: "Colorimetric Test for Fast Detection of SARS-CoV-2 in Nasal and Throat Swabs"

RR:C19 Evidence Scale rating by reviewer:

• Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.

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Review:

The authors have used a “colorimetric test for fast detection of SARS-CoV-2 in Nasal and Throat swabs. I must admit that the authors have taken a nice approach to the virus-detection using the most well-known technique the use of gold nanoparticles (AUNP). AUNP is one of the most commonly used nanoparticles, which is known for decades as a high-quality nanoparticle-based sensor because of its easy synthesis process, very low toxicity, and ease to functionalize. The authors have successfully synthesized the AUNP within the size range of 20nm and then functionalized it with the specific antibody for the three different virus proteins namely spike, membrane, and envelope proteins. The data also presented nicely. However, in terms of technology transfer and utilizing the developed sensor for the mass detection of the SARS-CoV-2 virus, the following few comments may be useful.

1. Although the data represented in Figure 1 suggested the possible binding of AUNP to the SERS-CoV-2 virus, the specificity and selectivity should be checked in presence of other viruses or similar strains so that it is not giving any false-positive results.

2. In addition, the efficiency of detection of the individual virus proteins should be checked, so that the real efficiency of the AUNP for a particular virus protein could be verified. Finally, based on the result it could be concluded whether the AUNP is equally efficient for all the proteins detection or not. This will really help to modify the sensor according to the need. The quantification of a load of individual antibodies to the AUNP may be helpful in this case.

3. The color change shown in Figures 1a and 1b upon binding to the virus will not be enough when one has a very less amount of virus signal.

4. The real quantification of the virus to a single AUNP should be verified. I may be wrong, however, the scheme shown in Figure 1 represents the number of AUNP attached to a single virus particle, I was expecting the reverse i.e. the number of virus particles to a single AUNP. I think it will help to understand the sensitivity of the AUNP sensor. These are all my suggestion. The authors may or may not take these works to be carried forward. However, It would be really nice, if a sensor like the authors presented in this manuscript, to have in the market. It will really be beneficial for society in the most difficult situation.