Volume 8(4): 048-057 (2016) - 048
J Bioanal Biomed
ISSN: 1948-593X JBABM, an open access journal
Open Access
Nandi et al., J Bioanal Biomed 2016, 8:4
DOI: 10.4172/1948-593X.1000152
Research Article Open Access
Journal of
Bioanalysis & Biomedicine
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ISSN: 1948-593X
Keywords: Swine infuenza H1N1; Angelicin compounds; Structural
descriptors; GA-MLR; QSAR; Molecular docking
Introduction
Swine infuenza is one of the viral family members of
Orthomyxoviridae. It contains ribonucleic acid (RNA) as genetic
component and has three serological types including A, B and C
respectively of which A subtype is a very virulent and infectious which
can attack to human [1]. Tis RNA virus contains hemagglutinin
(HA) and neuraminidase (NA) in the cell surface glycoproteins which
produces virulent efect. A number of 16 HA (H1 to H16) and 9 NA
(N1 to N9) are known in viral glycoproteins. Terefore, a total number
of 16 × 9=144 distinct progenies could be produced by combinatorial
combination of diferent types of HA and NA. Tese progenies may be
exemplifed by H1N1, H1N2…. , H2N1, H2N2…H3N2….H3N3.. and
so on. Currently, H1, H2 and H3 in combination with N1 and N2 are
most frequently dormant strains in human. Remaining subtypes are to
be zoonotic, causing disease mainly in fowl and nonhuman primates [2-
4]. Swine infuenza is originated in swine and easily picked up by wild
aquatic birds and other animal species like birds, pigs, ferret, horses,
seals, whales, mink, giant anteaters, cats and dogs in which infection is
largely intestinal, waterborne and asymptomatic. Ten the viral strains
emit to the roaming environment of these animals via nasal secretions,
saliva, cough, tears and intestinal diarrheal materials. Te reasserted
strains may infect to the humans adjacent proximity of these animals
and cross-infection occurs by transmitting of viral genetic mutant drif
[5] between humans and these animals. Tis may produce genetic re-
assortment of the viral strains which become very dangerous. Tis
genetically mutated drif can be speeded around the world and killed
almost 100 million people in 1918 in Spain due to H1N1 whereas H2N2
engulfed a number of 4 million people in 1957 in Asia. H3N3 caused
death of about one million people in Hong Kong in 1968, and in 2007
pathogenicity of H5N1 Avian infuenza strain caused global Health
threat. Currently in 2009, swine infuenza (H1N1) outbreak in Mexico
and other parts of the world has led to issuances of pandemic alertness
by the WHO [6,7]. According to WHO approximately 526,060 cases of
pandemic H1N1/09 infection and at least 6770 deaths were reported
all over the world by 15 November 2009. Tis has suddenly arisen in
North America and spread rapidly in Europe, Asia and South Africa
via human to human transmission within a very short span [8]. As
the devastating impact of swine infuenza is enormous, a renewed
drug discovery efort worldwide is essential to counteract the disease
more efciently. From the literature search it was shown that there is
no specifc chemotherapeutic agent against swine infuenza caused by
H1N1 viable strain. Terefore researchers have been trying to develop
anti swine infuenza chemotherapeutics which are able to combat
against swine infuenza pandemic.
A series of 1H-1,2,3-triazole-4-carboxamide compounds were
synthesized by Cheng et al. [9]. Tese compounds showed potent
biological activity against various strain of H3N2 and H1N1
infuenza virus as well as H5N1 (RG14) viral strain by inhibiting
the nuclear polymerization. Lepri et al. synthesized a number of
2-aminothiophene-3-carboxamide derivatives and evaluated their
biological activities against PA-PB1 interaction complex using Enzyme
Linked Immuno Sorbent Assay (ELISA) technique. It was found that
the viral polymerase consists of hetero trimetric complex consisting
of PB1, PB2 and PA sub units which are essential for transcription
and replication of viral m-RNA [10]. High throughput screening
confrmed that the angular furocoumarins which is also called as
angelicin can produce potent anti-viral activities. Further, Yeh and
co-workers synthesized a number of angelicin derivatives and tested
*Corresponding authors: Sisir Nandi, Division of Pharmaceutical Chemistry, Global
Institute of Pharmaceutical Education and Research, Uttarakhand Technical Univer-
sity, Kashipur-244713, India, Tel: +91 7500458478; E-mail: sisir.iicb@gmail.com
Received July 04, 2016; Accepted July 19, 2016; Published July 26, 2016
Citation: Alam M, Nandi S (2016) QSAR and Structure Based Molecular Docking
of Angelicin Compounds: an Attempt to Drug Design against Swine Infuenza. J
Bioanal Biomed 8: 048-057. doi:10.4172/1948-593X.1000152
Copyright: © 2016 Alam M, et al. This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited.
Abstract
There has been a great challenge of research and discovery of novel medicinal leads against swine infuenza since 2009.
Rational drug design utilizing pharmacoinformatics tools has been augmented now-a-days for in-silico screening of lead compounds
prior to experimental synthesis, structural elucidation, biological evaluation and fnally clinical trials to make the cost effcient drug
design and discovery research. There is hardly any specifc chemotherapeutics for the treatment against deadly swine infuenza
viral infection. Therefore, it is an urgent need to design and develop new anti-viral lead compounds active against swine infuenza.
Quantitative structure activity relationship (QSAR) has been used to develop models that correlate biological activity of angelicin
compounds derived from published literature and their computed structural properties. The approach started by generation of a series
of descriptors including topological, three dimensional, constitutional, functional groups and atom fragment indices respectively solely
calculated from the compounds in the data set. In this study, data set consists of 53 angelicin compounds along with their inhibitory
concentration 50% (IC50, μM) against H1N1 swine infuenza virus. Genetic algorithm-multiple linear regression (GA-MLR) analysis
technique has been to generate a number of QSAR models. The models were validated statistically incorporating training and test
set approaches. Finally, structure-based molecular docking study has been performed for interpretation of the mode of binding of the
angelicin compounds toward H1N1 target. QSAR and molecular docking analysis of these congeners have not yet been reported.
Therefore, this study has signifcant impact for designing of the highly active compounds in this series that are useful for the treatment
of swine infuenza. In-silico structure based docking model could be helpful for design and screening of congeneric compounds
having mode of binding similarity.
QSAR and Structure Based Molecular Docking of Angelicin Compounds:
an Attempt to Drug Design against Swine Influenza
Muneer Alam and Sisir Nandi*
Global Institute of Pharmaceutical Education and Research, Uttarakhand Technical University, India