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. 2024 Jun 25:12:655.
doi: 10.12688/f1000research.134956.2. eCollection 2023.

In silico screening for potential inhibitors from the phytocompounds of Carica papaya against Zika virus NS5 protein

Kishore Krishna Kumaree  1   2 , Naga Venkata Anusha Anthikapalli  3 , Anchalee Prasansuklab  1   2
Affiliations

In silico screening for potential inhibitors from the phytocompounds of Carica papaya against Zika virus NS5 protein

Kishore Krishna Kumaree et al. F1000Res. .

Abstract

Background: The Zika virus (ZIKV) infection has emerged as a global health threat. The causal reasoning is that Zika infection is linked to the development of microcephaly in newborns and Guillain-Barré syndrome in adults. With no clinically approved antiviral treatment for ZIKV, the need for the development of potential inhibitors against the virus is essential. In this study, we aimed to screen phytochemicals from papaya ( Carica papaya L.) against NS5 protein domains of ZIKV.

Methods: Approximately 193 phytochemicals from an online database (IMPACT) were subjected to molecular docking using AutoDock Vina against the NS5-MTase protein domain (5WXB) and -RdRp domain (5U04).

Results: Our results showed that β-sitosterol, carpaine, violaxanthin, pseudocarpaine, Δ7-avenasterols, Rutin, and cis-β-carotene had the highest binding affinity to both protein domains, with β-sitosterol having the most favorable binding energy. Furthermore, ADMET analysis revealed that selected compounds had good pharmacokinetic properties and were nontoxic.

Conclusions: Our findings suggest that papaya-derived phytochemicals could be potential candidates for developing antiviral drugs against ZIKV. However, further experimental studies using cell lines and in vivo models are needed to validate their efficacy and safety.

Keywords: AutoDoc Vina; Molecular docking; Papaya; Zika virus.

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Conflict of interest statement

No competing interests were disclosed.

Figures

Figure 1.
Figure 1.. The surface, structural, and non-structural proteins of the ZIKV are illustrated in the diagram, which highlights the virion components and the genomic RNA.
The ZIKV polyprotein is composed of seven non-structural proteins (NS1, NS2A, NS2B, NS3 protease and helicase domains, NS4A, NS4B, NS5 methyltransferase, and RNA polymerase domains) and three structural proteins (C, M, and E). In addition, NS5 methyltransferase and RNA polymerase domains’ structures were retrieved from PDB (Protein Data Bank) databases.
Figure 2.
Figure 2.. Structural representation (2D) of the ligands shortlisted for having greater binding affinity to the receptor than the positive ligands used (Sofosbuvir and Sinefungin for 5U04 and 5WXB, respectively).
Figure 3.
Figure 3.. Docking results of phytocompounds from C. papaya against target NS5 protein domains NS5-MTase (5WXB) and NS5-RdRp (5U04) of Zika virus (A) The Heatmap showing the binding affinities of best-docked compounds with target protein domains. Blue indicates low binding affinity and red indicates high binding affinity. (B) Venn diagram representing the commonly shared best-docked ligands (compared to respective positive control ligands) with the target protein domains.
Figure 4.
Figure 4.. 2D and 3D interaction views of the best-docked phytocompounds from C. papaya, illustrating their binding modes with ZIKV NS5 protein domains. (A)-(G) display the complexes with MTase-5WXB, (H)-(N) present the complexes with RdRp-5U04, and (O)-(P) show the complexes with positive controls sinefungin and sofosbuvir.
Figure 4.
Figure 4.. 2D and 3D interaction views of the best-docked phytocompounds from C. papaya, illustrating their binding modes with ZIKV NS5 protein domains. (A)-(G) display the complexes with MTase-5WXB, (H)-(N) present the complexes with RdRp-5U04, and (O)-(P) show the complexes with positive controls sinefungin and sofosbuvir.
Figure 4.
Figure 4.. 2D and 3D interaction views of the best-docked phytocompounds from C. papaya, illustrating their binding modes with ZIKV NS5 protein domains. (A)-(G) display the complexes with MTase-5WXB, (H)-(N) present the complexes with RdRp-5U04, and (O)-(P) show the complexes with positive controls sinefungin and sofosbuvir.
Figure 4.
Figure 4.. 2D and 3D interaction views of the best-docked phytocompounds from C. papaya, illustrating their binding modes with ZIKV NS5 protein domains. (A)-(G) display the complexes with MTase-5WXB, (H)-(N) present the complexes with RdRp-5U04, and (O)-(P) show the complexes with positive controls sinefungin and sofosbuvir.
Figure 4.
Figure 4.. 2D and 3D interaction views of the best-docked phytocompounds from C. papaya, illustrating their binding modes with ZIKV NS5 protein domains. (A)-(G) display the complexes with MTase-5WXB, (H)-(N) present the complexes with RdRp-5U04, and (O)-(P) show the complexes with positive controls sinefungin and sofosbuvir.
Figure 4.
Figure 4.. 2D and 3D interaction views of the best-docked phytocompounds from C. papaya, illustrating their binding modes with ZIKV NS5 protein domains. (A)-(G) display the complexes with MTase-5WXB, (H)-(N) present the complexes with RdRp-5U04, and (O)-(P) show the complexes with positive controls sinefungin and sofosbuvir.
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Grants and funding

C2F (Secondary Century Fund) Postdoctoral Fellowship, Chulalongkorn University, Bangkok 10330