DOI: 10.4018/IJQSPR.2018070101
International Journal of Quantitative Structure-Property Relationships
Volume 3 • Issue 2 • July-December 2018
Copyright © 2018, IGI Global. Copying or distributing in print or electronic forms without written permission of IGI Global is prohibited.
1
First Report on the Validated
Classifcation-Based Chemometric
Modeling of Human Rhinovirus 3C
Protease (HRV 3Cpro) Inhibitors
Sk. Abdul Amin, Jadavpur University, Kolkata, India
Nilanjan Adhikari, Jadavpur University, Kolkata, India
Shovanlal Gayen, Dr. Harisingh Gour University, Sagar, India
Tarun Jha, Jadavpur University, Kolkata, India
ABSTRACT
Human rhinoviruses (HRVs), a major cause of common cold and upper respiratory infections, may
trigger severe respiratory complications like asthma and COPD. To date, no drugs are available in the
market which are designed as novel HRV inhibitors despite the involvement of some pharmaceutical
companies’ due to economical and clinical constraints. HRV 3C protease may be a potential target for
drug design as it plays crucial role in viral RNA replication and virion assembly process. Therefore,
designing novel HRV 3Cpro inhibitors is necessary and demanding in the field of antiviral drug design.
In this article, statistically significant and validated classification-based QSARs of a series of HRV
3Cpro inhibitors were performed for the first time as per the authors’ knowledge. Results suggest that
oxopyrrolidine and piperidinone rings are favored whereas carboxybenzyl and unsubstituted benzyl
functions may be unfavorable. Moreover, this group, along with cyclic alkyl or aryl ring structures
may favor HRV 3Cpro inhibition. These observations may be utilized for the design of a higher active
anti-HRV agent in future.
KeywoRdS
Bayesian Classification Model, Bayesian Fingerprint, Classification-Based QSAR, Human Rhinovirus 3C
Protease Inhibitors, Linear Discriminant Analysis
INTRodUCTIoN
Human rhinoviruses (HRVs), belonging to the family of picornavirus, play a significant role in
causing common cold and upper respiratory infections that has a great impact on the health and
economy worldwide (Simasek & Blandino, 2007; DePlama, Vliegen, DeClercg & Neyts, 2008;
Jensen, Walker, Jans & Ghildyal, 2015; Kawatkar et al., 2016). Although the infection is generally
mild and self-limiting, HRV infection may precipitate severe respiratory complications such as asthma
exacerbations and chronic obstructive pulmonary disease (COPD) (Message et al., 2008; Denlinger
et al., 2011; O’Bryne, 2011; Baxter et al., 2011). Therefore, it may be assumed that prevention and
early treatment against the HRV infections may impart some beneficial effects (Gwaltney, Winther,
Patrie & Hendly, 2002; Kawatkar et al., 2016). In the United States alone, an estimated cost related to
the cold surpassed $40 billion during 2003 (Schuneman et al., 2014). Therefore, major challenges and
interests are lying in the discovery process of anti-HRV drugs by pharmaceutical industries (Binford