Structure-based identification of small molecules against influenza A virus endonuclease: an in silico and in vitro approach

Sai Disha, K and Puranik, Rashmi and Sudheesh, N and Kavitha, K and Fathima, Fajeelath and Anu, KR and Joseph, Alex and Anitha, J and Arunkumar, G and Mudgal, Piya Paul (2020) Structure-based identification of small molecules against influenza A virus endonuclease: an in silico and in vitro approach. Pathogens and Disease, 78 (4). pp. 1-10. ISSN 2049-632X

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Abstract

Influenza viruses are known to cause acute respiratory illness, sometimes leading to high mortality rates. Though there are approved influenza antivirals available, their efficacy has reduced over time, due to the drug resistance crisis. There is a perpetual need for newer and better drugs. Drug screening based on the interaction dynamics with different viral target proteins has been a preferred approach in the antiviral drug discovery process. In this study, the FDA approved drug database was virtually screened with the help of Schr ¨ odinger software, to select small molecules exhibiting best interactions with the influenza A virus endonuclease protein. A detailed cytotoxicity profiling was carried out for the two selected compounds, cefepime and dolutegravir, followed by in vitro anti-influenza screening using plaque reduction assay. Cefepime showed no cytotoxicity up to 200 μM, while dolutegravir was non-toxic up to 100 μM in Madin–Darby canine kidney cells. The compounds did not show any reduction in viral plaque numbers indicating no anti-influenza activity. An inefficiency in the translation of the molecular interactions into antiviral activity does not necessarily mean that the molecules were inactive. Nevertheless, testing the molecules for endonuclease inhibition per se can be considered a worthwhile approach

Item Type: Article
Uncontrolled Keywords: Influenza virus; Polymerase acidic subunit; Virtual screening; Molecular docking Influenza virus; Polymerase acidic subunit; Virtual screening; Molecular docking
Subjects: Departments at MU > Manipal Centre for Virus Research
Pharmacy > MCOPS Manipal > Pharmaceutical Chemistry
Depositing User: KMC Library
Date Deposited: 03 Nov 2020 08:47
Last Modified: 03 Nov 2020 08:47
URI: http://eprints.manipal.edu/id/eprint/155971

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