Natural Compounds as Non-Nucleoside Inhibitors of Zika Virus Polymerase through Integration of In Silico and In Vitro Approaches
, Melina Mottin 1,†, Caroline Sprengel Lima 2, LetÃcia R. Assis 2, Ketllyn Zagato de Oliveira 3, Nathalya Cristina de Moraes Roso Mesquita 3, Natasha Marques Cassani 4, Igor Andrade Santos 4, Joyce Villa Verde Bastos Borba 1, VinÃcius Alexandre Fiaia Costa 1, Bruno Junior Neves 1, Rafael Victorio Carvalho Guido 3, Glaucius Oliva 3, Ana Carolina Gomes Jardim 4, Luis Octávio Regasini 2,* and Carolina Horta Andrade 1,*Round 1
Reviewer 1 Report
Ramos et al. performed a computational screening for inhibitors against Zika virus NS5 RdRp and selected 9 molecular hits for further validation and characterization of antiviral activity. Out of these 9 hits, pedalitin and quercetin inhibited NS5 RdRp with low micromolar activity in vitro and displayed modest antiviral activity in cell-based assays. The authors also rationalized the binding mode of pedalitin and quercetin by molecular docking. These inhibitors provide a scaffold for potential optimization of potency activity. Overall this is a well written manuscript and can be published as it is.
Author Response
Thank you for your appreciation of our work.
Reviewer 2 Report
The manuscript titled Natural compounds as non-nucleoside inhibitors of Zika virus polymerase through integration of in silico and in vitro approaches by authors et al. demonstrated that the potential of the natural compound pedalitin as a candidate for structural optimization studies toward the discovery of new anti-ZIKV drug candidates. In general, this paper seems to be quite interesting and I would like to recommend the acceptance of this work provided that authors can well address the following questions.
1. The authors should provide more visual evaluation results, such as immunofluorescence of viral proteins or genetic assays, to make the activity assay more convincing.
2. The virus-host cell interactions are receiving increasing attention, and in addition to studying the direct interaction of drugs with ZIKV viral proteins, authors may also consider studying antiviral drugs from the intervention of virus-host interactions, please discuss in the future prospect, anyway, it has an important role in viral resistance and unknown emergent viral infections.
Author Response
Please see the attachment.
Author Response File: 
Author Response.docx
