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.

In-vitro antiviral activity and in-silico targeted study of quinoline-3-carboxylate derivatives against SARS-Cov-2 isolate / R.K. Mittal, P. Purohit, M. Sankaranarayanan, M. Muzaffar-Ur-Rehman, D. Taramelli, L. Signorini, M. Dolci, N. Basilico. - In: MOLECULAR DIVERSITY. - ISSN 1381-1991. - (2023), pp. 1-15. [Epub ahead of print] [10.1007/s11030-023-10703-w]

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

D. Taramelli;L. Signorini;M. Dolci
Penultimo
;
N. Basilico
Ultimo
2023

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.
Anti-viral drugs; Molecular dynamics; Protease inhibitors; SARS-CoV-2; Targeted anti-viral
Settore MED/04 - Patologia Generale
   Piano di Sostegno alla Ricerca 2015-2017 - Linea 2 "Dotazione annuale per attività istituzionali" (anno 2019)
   UNIVERSITA' DEGLI STUDI DI MILANO
2023
22-lug-2023
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1004370
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