Pyrazine-chromene-3-carbohydrazide conjugates: Molecular docking and ADMET predictions on dual- acting compounds against SARS-CoV-2 Mpro and RdRp

Arif Mermer; Serhii Vakal

Pyrazine-chromene-3-carbohydrazide conjugates: Molecular docking and ADMET predictions on dual- acting compounds against SARS-CoV-2 Mpro and RdRp

Abstract

Drug discovery campaigns against COVID-19 lag far behind vaccine development, but given the low vaccine production rate and unfair distribution, there is still an urgent need to advance reliable and potent anti-SARS- CoV-2 agents. We aimed to identify novel and effective molecules with dual-target activity against SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA-polymerase (RdRp). For this, we designed and evaluated the library of hybrid compounds based on pyrazine and 4H-chromen-4-one linked by amide bridges. The synthetic availability of the compounds ranged from 3.08 to 3.40, indicating that these compounds are easy to synthesize. According to in silico ADMET prediction, most of the compounds satisfied all rules of drug-likeness. Compounds CPC-2, 3, 4, 8, 10, 11-14, and 16 were CYP1A2, CYP2C9, and CYP3A4 inhibitors, whereas none of them inhibited CYP2C19 and CYP2D6 isoforms. All designed compounds were predicted to be well-absorbed in the GI tract but not blood-brain barrier permeant and not subject to active efflux. Molecular docking studies against SARS-CoV-2 Mpro showed that compounds CPC-1, 6, 7, 8, and 10 could establish multiple H-bonds with the binding site residues. In the case of SARS-CoV-2 RdRp, compounds CPC-5, 6, 8, 13, 14, and 16 had the most favorable binding orientations and could establish H-bonds, pi-cation, and salt-bridges with the binding tunnel residues and RNA. Compound CPC-6 turned to be the most promising candidate from the dual-action side since it had reasonable docking scores and MM-GBSA ∆Gbind values, and good interaction profiles for both Mpro and RdRp.

Keywords

References

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Details

Primary Language

English

Subjects

Pharmaceutical Chemistry

Journal Section

Research Article

Authors

Arif Mermer ^*
Türkiye

Serhii Vakal This is me
Finland

Publication Date

June 28, 2025

Submission Date

April 28, 2021

Acceptance Date

November 18, 2021

Published in Issue

Year 2021 Volume: 25 Number: 6

IZ

https://izlik.org/JA39DZ48AZ

Cite

RIS / Bibtex

APA

Mermer, A., & Vakal, S. (2025). Pyrazine-chromene-3-carbohydrazide conjugates: Molecular docking and ADMET predictions on dual- acting compounds against SARS-CoV-2 Mpro and RdRp. Journal of Research in Pharmacy, 25(6), 953-966. https://izlik.org/JA39DZ48AZ

AMA

1.Mermer A, Vakal S. Pyrazine-chromene-3-carbohydrazide conjugates: Molecular docking and ADMET predictions on dual- acting compounds against SARS-CoV-2 Mpro and RdRp. J. Res. Pharm. 2025;25(6):953-966. https://izlik.org/JA39DZ48AZ

Chicago

Mermer, Arif, and Serhii Vakal. 2025. “Pyrazine-Chromene-3-Carbohydrazide Conjugates: Molecular Docking and ADMET Predictions on Dual- Acting Compounds Against SARS-CoV-2 Mpro and RdRp”. Journal of Research in Pharmacy 25 (6): 953-66. https://izlik.org/JA39DZ48AZ.

EndNote

Mermer A, Vakal S (July 1, 2025) Pyrazine-chromene-3-carbohydrazide conjugates: Molecular docking and ADMET predictions on dual- acting compounds against SARS-CoV-2 Mpro and RdRp. Journal of Research in Pharmacy 25 6 953–966.

IEEE

[1]A. Mermer and S. Vakal, “Pyrazine-chromene-3-carbohydrazide conjugates: Molecular docking and ADMET predictions on dual- acting compounds against SARS-CoV-2 Mpro and RdRp”, J. Res. Pharm., vol. 25, no. 6, pp. 953–966, July 2025, [Online]. Available: https://izlik.org/JA39DZ48AZ

ISNAD

Mermer, Arif - Vakal, Serhii. “Pyrazine-Chromene-3-Carbohydrazide Conjugates: Molecular Docking and ADMET Predictions on Dual- Acting Compounds Against SARS-CoV-2 Mpro and RdRp”. Journal of Research in Pharmacy 25/6 (July 1, 2025): 953-966. https://izlik.org/JA39DZ48AZ.

JAMA

1.Mermer A, Vakal S. Pyrazine-chromene-3-carbohydrazide conjugates: Molecular docking and ADMET predictions on dual- acting compounds against SARS-CoV-2 Mpro and RdRp. J. Res. Pharm. 2025;25:953–966.

MLA

Mermer, Arif, and Serhii Vakal. “Pyrazine-Chromene-3-Carbohydrazide Conjugates: Molecular Docking and ADMET Predictions on Dual- Acting Compounds Against SARS-CoV-2 Mpro and RdRp”. Journal of Research in Pharmacy, vol. 25, no. 6, July 2025, pp. 953-66, https://izlik.org/JA39DZ48AZ.

Vancouver

1.Arif Mermer, Serhii Vakal. Pyrazine-chromene-3-carbohydrazide conjugates: Molecular docking and ADMET predictions on dual- acting compounds against SARS-CoV-2 Mpro and RdRp. J. Res. Pharm. [Internet]. 2025 Jul. 1;25(6):953-66. Available from: https://izlik.org/JA39DZ48AZ