Comments on abstract, title, references

Abstract: The abstract outlines the SARS- CoV-2 pandemic issue. Then it goes on to address the importance of 3CLpro enzyme in the treatment of SARS- CoV-2. The methodology could have been given in a sequence for more clarity along with the newly identified top 10 ligands with their medical applications.

Title: The investigation is based on insilico methods, hence it can be included. Since there is an insurgence to identify novel drugs a few phytoconstituents/bioactive compounds names would have been listed/mentioned.

References: upto date

Comments on introduction/background

The introductory part provides the latest information about the SARS- CoV-2 pandemic across the world. A review of the literature on the same lines of the investigation should have been stated with examples, while it was addressed in a single sentence. Similarly, medicinally important phytoconstituents/bioactive compounds should have been included to give wider knowledge to the researchers/readers as it forms the purpose of this study.

Comments on methodology

A detailed methodology with appropriate subsections was given. In primary structure analysis of a protein sequence, the physicochemical properties to be placed before multiple sequences analysis which will provide more insights in deciphering the significance of a protein sequence.

Comments on data and results

The data and results are exhaustive with relevant figs and tables. However, I have a few comments pertaining to the structural domains of the predicted model. It will be good if the authors provide a Figure showing different domains right from the N-C terminal in the form of a linear sequence.

In molecular docking, the protein-ligand interactions can be represented (Figure & Table) along with their atomic length measurements to verify the closeness between the docked complexes (<3 Angstrom).

Similarly, the authors can also mention the safety (toxicity), efficacy, and stability of the newly identified anti-covid drugs.

Comments on discussion and conclusions

The discussion part is well dealt with adequate references. To my surprise, I would like to recall that Shikimic acid or star anise was not listed in top 10 of the identified novel plant source compounds. Since Oseltamavir or Tamiflu is also recommended to treat SARS- CoV-2 which is mainly extracted as Shikimic acid/shikimate (a phytoconstituent) from star anise.

The conclusion is well written and addresses the significance of newly identified compounds based on insilico analysis.