@article{6b781d1467434482b5ce74d19514fc93,
title = "A novel compound active against SARS-CoV-2 targeting uridylate-specific endoribonuclease (NendoU/NSP15):: In silico and in vitro investigations",
abstract = "NendoU (NSP15) is an Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2′-3′-cyclic phosphates 5′ to the cleaved bond. Our in-house library was subjected to high throughput virtual screening (HTVS) to identify compounds with potential to inhibit NendoU enzyme, high-rank compounds (those that bound to multiple target structures) were further subjected to 100 nanoseconds MD simulations. Among these, one was found to be bound highly stable within the active site of the NendoU protein structure. Here, we are reporting a derivative of piperazine based '(2S,3S)-3-amino-1-(4-(4-(tert-butyl)benzyl)piperazin-1-yl)-4-phenylbutan-2-ol' (IV) from our in-house libraries having potential efficacy against SARS-CoV-2 in in vitro assays. This compound demonstrated inhibition of viral replication at the same level as Ivermectin, a known SARS-CoV-2 inhibitor, which is not used due to its toxicity at a higher than the currently approved dosage. Compound IV was not toxic to the cell lines up to a 50 μM concentration and exhibited IC50s of 4.97 μM and 8.46 μM in viral entry and spread assay, respectively. Therefore, this novel class of NendoU inhibitor could provide new insights for the development of treatment options for COVID-19.",
author = "Sumit Kumar and Yash Gupta and Zak, {Samantha E.} and Charu Upadhyay and Neha Sharma and Herbert, {Andrew S.} and Ravi Durvasula and Vladimir Potemkin and Dye, {John M.} and Poonam and Prakasha Kempaiah and Brijesh Rathi",
note = "Funding Information: Part of this work was supported by the DST (DST/INT/BRICS/COVID-19/2020), RFBR, CNPq and SAMRCA [grant number 20-53-80002] under BRICS multilateral project. Authors are thankful to the Division of Infectious Diseases, Mayo Clinic, Jacksonville for supporting the Drug Discovery Program and the High Computing Platform. SK, CU and NS are thankful to council of scientific and industrial research (CSIR), New Delhi for providing senior research fellowship. Opinions, discussions, conclusions, interpretations, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army. The mention of trade names or commercial products does not constitute endorsement or recommendation for use by the Department of the Army or the Department of Defence. Funding Information: Part of this work was supported by the DST (DST/INT/BRICS/ COVID-19/2020), RFBR, CNPq and SAMRCA [grant number 20-53-80002] under BRICS multilateral project. Authors are thankful to the Division of Infectious Diseases, Mayo Clinic, Jacksonville for supporting the Drug Discovery Program and the High Computing Platform. SK, CU and NS are thankful to council of scientific and industrial research (CSIR), New Delhi for providing senior research fellowship. Opinions, discussions, conclusions, interpretations, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Publisher Copyright: {\textcopyright} The Royal Society of Chemistry.",
year = "2021",
month = oct,
doi = "10.1039/d1md00202c",
language = "English (US)",
volume = "12",
pages = "1757--1764",
journal = "RSC Medicinal Chemistry",
issn = "2040-2503",
publisher = "Royal Society of Chemistry",
number = "10",
}