creators_name: Kaur, Simran
creators_name: Brar, Deshkanwar S.
creators_name: Joshi, Akshay
creators_name: Singh, Nittu
creators_name: Chawla, Ravneet S.
creators_name: Kumar, Sahil
creators_name: Dhiman, Sumit
creators_name: Nandi, Utpal
creators_name: Ringe, Rajesh P.
creators_name: Thakur, Krishan G.
creators_name: Chaudhari, Vinod D.
type: article
datestamp: 2026-07-13 08:24:50
lastmod: 2026-07-13 08:24:50
metadata_visibility: show
title: Development of Benzimidazole-Based BZ-30 as an Orally Bioavailable Broad-Spectrum Inhibitor of SARS-CoV-2
ispublished: pub
subjects: QR
note: Copyright to this article belongs to AMER CHEMICAL SOC
abstract: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiological agent of the 2019 global pandemic, continues to undermine therapeutic interventions due to its high transmissibility and mutability. This highlights the need for potent antivirals capable of combating emerging variants and controlling outbreaks. Here, we report the discovery and development of the first-in-class novel benzimidazole (BZ) derivatives as potent inhibitors of SARS-CoV-2. Through antiviral screening, the benzimidazolone derivative (I) was found as the hit. Further hit-to-lead optimization led to BZ compounds with submicromolar IC50 values. Mechanistically, these compounds partially inhibit endocytosis entry pathways. The compounds shortlisted have broad-spectrum antiviral profiles against different variants of concern. Notably, BZ-01 and BZ-30 show good pharmacokinetic properties, with BZ-30 displaying excellent oral bioavailability. Evaluation of BZ-30 in SARS-CoV-2-challenged hamsters significantly reduced viral load and improved lung pathology, indicating its in vivo antiviral efficacy and highlighting its therapeutic potential as an orally available antiviral candidate.
date: 2026-04-13
date_type: published
publication: JOURNAL OF MEDICINAL CHEMISTRY
volume: 69
number: 8
publisher: AMER CHEMICAL SOC
place_of_pub: 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
pagerange: 9537-9557
refereed: TRUE
official_url: https://pubs.acs.org/doi/10.1021/acs.jmedchem.6c00365
citation:   Kaur, Simran and Brar, Deshkanwar S. and Joshi, Akshay and Singh, Nittu and Chawla, Ravneet S. and Kumar, Sahil and Dhiman, Sumit and Nandi, Utpal and Ringe, Rajesh P. and Thakur, Krishan G. and Chaudhari, Vinod D.  (2026) Development of Benzimidazole-Based BZ-30 as an Orally Bioavailable Broad-Spectrum Inhibitor of SARS-CoV-2.  JOURNAL OF MEDICINAL CHEMISTRY, 69 (8).  pp. 9537-9557.      
document_url: http://crdd.osdd.net/open/3458/1/references%20%286%29.bib