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In-vitro antiviral activity and in-silico targeted study of quinoline-3-carboxylate derivatives against SARS-Cov-2 isolate

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Abstract

In recent years, the viral outbreak named COVID-19 showed that infectious diseases have a huge impact on both global health and the financial and economic sectors. The lack of efficacious antiviral drugs worsened the health problem. Based on our previous experience, we investigated in vitro and in silico a series of quinoline-3-carboxylate derivatives against a SARS-CoV-2 isolate. In the present study, the in-vitro antiviral activity of a series of quinoline-3-carboxylate compounds and the in silico target-based molecular dynamics (MD) and metabolic studies are reported. The compounds’ activity against SARS-CoV-2 was evaluated using plaque assay and RT-qPCR. Moreover, from the docking scores, it appears that the most active compounds (1j and 1o) exhibit stronger binding affinity to the primary viral protease (NSP5) and the exoribonuclease domain of non structural protein 14 (NSP14). Additionally, the in-silico metabolic analysis of 1j and 1o defines CYP2C9 and CYP3A4 as the major P450 enzymes involved in their metabolism.

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Acknowledgements

All authors gives the special thanks to NIPER Mohali, Dr Bhutani lab, for initiating project and granted by his name for the help of the, synthesis, and characterization (Part of Ravi Mittal PhD thesis) and PP thanks to Graphic Era Hill university, Dehradun for providing seed money and giving the space and RKM thanks to NIPER Mohali for initiating the results and giving space for his PhD work.

Funding

Thanks to DBT: BT/PR5634/MED/29/623/2012 and ICMR: 5/7/827/12-RCH for financial support (Under the ownership of the project Late Prof K. K. Bhutani). This work was partially funded by PSR2019 to NB by the University of Milan.

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Authors and Affiliations

  1. National Institute of Pharmaceutical Education and Research, S A S Nagar Mohali, Punjab, 160062, India

    Ravi Kumar Mittal

  2. Galgotias College of Pharmacy, Greater Noida, UttarPradesh, India

    Ravi Kumar Mittal

  3. School of Pharmacy, Graphic Era Hill University, Dehradun, Uttarakhand, 248002, India

    Priyank Purohit

  4. Medicinal Chemistry Research Laboratory, Department of Pharmacy, BITS Pilani, Pilani Campus, Pilani, Rajasthan, 333031, India

    Murugesan Sankaranarayanan & Mohammed Muzaffar-Ur-Rehman

  5. Department of Pharmacological and Biomolecular Sciences, University of Milan, Pascal Street 36, 20133, Milan, Italy

    Donatella Taramelli

  6. Department of Biomedical, Surgical and Dental Sciences, University of Milan, Pascal Street 36, 20133, Milan, Italy

    Lucia Signorini, Maria Dolci & Nicoletta Basilico

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  1. Ravi Kumar Mittal
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  2. Priyank Purohit
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  6. Lucia Signorini
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  8. Nicoletta Basilico
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Contributions

RKM: Conceptualization, Methodology, synthesis (Under the guidance of Dr. Bhautani). PP: Validation, Formal analysis, Writing—original draft. MS and MM-U-R: In silico docking and MD studies, method and validation, with drafting of the said part. DT: Draft finalization and revision. LS, and MD:Assays for antiviral activity, methodology, review of the manuscript. NB: supervision of the antiviral assays, writing, analysis and finalization of the manuscript.

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Correspondence to Priyank Purohit.

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Mittal, R.K., Purohit, P., Sankaranarayanan, M. et al. In-vitro antiviral activity and in-silico targeted study of quinoline-3-carboxylate derivatives against SARS-Cov-2 isolate. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10703-w

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