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AbstractThe protein galectin, which binds to carbohydrates and is involved in a number of therapeutic processes including cell proliferation, inflammatory responses, apoptosis, etc., has been discovered as a potential therapeutic target. Galectin-3 is a stable biomarker that exhibits both increased and decreased expression in a variety of illnesses and infections, regardless of sex, age, or body mass index. The goal of the current study is to apply bioinformatics techniques to examine the possibility of cardiovascular medications to inhibit Galectin-3-related biological activities. Unsupervised clustering techniques, molecular docking, and guided molecular dynamics (MD) simulation were used to create a computational pipeline that was used to screen potential chemical compounds from a library of chemical compounds with related molecular fingerprints. Utilizing input factors such as gene expression, mode of action, and chemical descriptors, clustering enables prioritization of medicinal molecules. Twenty-four compounds were screened and repurposed against Galectin-3 utilizing molecular docking as part of the cluster-facilitated virtual screening technique. The polar interactions that Arg144, Glu184, Arg162, His158, and Asn174 have with Bufalin, Cymarin, and Ouabalin have the highest binding affinities, according to docking studies. Studies using MD simulations confirm the tested compounds’ ability to inhibit Galectin-3. Galactin-3 targeted experimental and in vivoanimal model-based validation studies using Bufalin, Cymarin, and Ouabalin are also necessary.Communicated by Ramaswamy H. Sarma

AbstractThe global emergence of novel coronavirus disease and its rapid global expansion over a short span of time require effective countermeasures to combat it. Development of a specific vaccine can induce an optimal antibody response, thus providing immunity against it. Our study proposes a detailed and comprehensive immunoinformatic approach that can be applied to the currently available coronavirus protein data in the online server for vaccine candidate development. We have identified the receptor binding domain (RBD) of structural spike protein (S1) as a potential target for immunity against COVID- 19 infection. Epitope prediction illustrated cytotoxic T-cell epitopes, helper T-cell epitopes, and B-cell epitopes associated with the target protein. These were joined through specific linkers along with adjuvant beta-defensin located at the N-terminal to create a multi epitope subunit vaccine (MESV). The specificity in the binding of the devised vaccine candidate to the TLR-3 immune cell receptor was evaluated via molecular docking interaction studies. Good docking score combined with robust interactions in the binding cavity certified the stringency of the engineered vaccine. Molecular dynamics simulation data showed minimal variation of the root-mean square deviations (RMSDs) and root-mean-square fluctuations (RMSFs) which confirmed the interaction stability. These results obtained from various in-silicoexperiments indicate the potency of this vaccine candidate as a probable therapeutic agent against COVID-19. Vaccination strategies targeting conserved epitope-based immune response would be beneficial in providing cross protection across beta-coronaviruses, and such vaccines would be resistant to the ever-evolving viruses.Communicated by Ramaswamy H. Sarma

AbstractIn this study, attempts have been made to identify novel inhibitor(s) of SdiA (a homolog of LuxR transcription regulator) of Klebseilla pneumoniaeusing various computational techniques. 4LFU was used as a template to model the structure of SdiA. ProCheck, Verify3D, Ramachandran plot scores and ProSA-Web confirmed the good quality of the model as the root mean square deviation (RMSD) between SdiA model, and 4LFU template was estimated to be 0.21 Å. The secondary structural contents of SdiA model were predicted using PDBsum. The only binding site of SdiA was identified (area = 523.083 Å2and volume = 351.044 Å3) using CASTp. Molecular docking at three different levels [high throughput virtual screening, standard-precision (SP) and extra-precision (XP) dockings] with increasingly stringent conditions was performed using Glide on Selleck’s express pick library (L3600). A total of 61 ligands were found to bind with high affinities to the active site of SdiA. Further, the effect of solvent on protein-ligand interaction was evaluated by performing molecular mechanics-general born surface area (Prime/MM-GBSA). On the basis of Prime/MM-GBSA score, molecular dynamics simulation (50 ns) was performed on the ligand (WAY-390139-A) showing lowest binding energy to confirm the stability of protein-ligand complex. Docking energy and the corresponding binding affinity of WAY-390139-A towards SdiA were estimated to be –13.005 kcal mol–1and 3.46 × 109M−1, respectively. Our results confirm that WAY-390139-A binds at the autoinducer binding site of SdiA with high affinity and stability and can be further exploited as potential drug against K. pneumoniaeafter experimental validation.Communicated by Ramaswamy H. Sarma

AbstractCommunicated by Ramaswamy H. Sarma

AbstractGlipizide is known to stimulate insulin secretion by β-cells of the pancreas. It is a second-generation sulfonylurea drug used in the management of type 2 diabetes. The shorter biological half-life makes it a suitable candidate to be designed as a controlled release formulation. Human serum albumin (HSA), a major plasma protein plays a crucial role in the transportation of drugs, hormones, fatty acids, and many other molecules and determines their physiological fate and biodistribution. In this study, the interaction of glipizide with HSA was investigated under physiological conditions using multi-spectroscopic techniques corroborated with molecular docking and dynamics approach. It was found that glipizide integrates to HSA with a binding constant in the order of 105M−1. The mode of fluorescence quenching by glipizide is static in nature with one binding site. Glipizide preferentially interacts with sub-domain IIA of HSA and their complexion is thermodynamically favorable. This interaction results in the loss of α-helical content of HSA. The energy transfer efficiency from HSA to glipizide was found to be 26.72%. In silicomolecular docking and simulation studies ratified in vitrofindings and revealed that hydrogen bonds and hydrophobic interactions are accountable for glipizide-HSA complex formation.Communicated by Ramaswamy H. Sarma

The widespread burden of Dengue was amplified over the last three decades and almost half of the world population is estimated to be at the risk of Dengue fever, Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) which has increased drastically in recent times. Therefore, it has been a major concern of public health world wide. The genome of dengue virus encodes a single polyprotein; having both the functional and non-functional region. The predicted motif involved in regulation, activity and stability of virus and protein sub cellular localization of all structural regions of dengue virus variants were plasma membrane. Eight significant motifs like cAMP & cGMP dependent protein kinase, N-Glycosylation, N-Myristoylation, Protein kinase C, Casein kinase 2, GTP-Binding Elongation Factor Signature, Tyrosine kinase and Glycosaminoglycan were predicted in dengue variants. These finding might be used to distinguish the proteome function for targeting or designing the antiviral inhibitors against the motifs of Dengue virus. Keywords: Dengue, sub cellular localization, motifs, antiviral drugs, Table of Contents Abstract Introduction Material And Methods Results And Discussion References Introduction Dengue virus genome contains a positive strand RNA with one open reading frame coding for polyprotein. The [...]

Hexachlorocyclohexane (HCH) is a non-degradable compound extensively used against agricultural pests and various public health programs for controlling mosquitoes. It imbibes into the food chain from crop to animals; biodegradable enzymes present in the genes of some bacteria degrade HCH in soil. Mainly, two genes linA and linB encode dehydrochlorinase and dehalogenase enzymes involved in degradation of HCH. Bioinformatics strategies were used to find other homologous genes and proteins, which can also degrade HCH present in various bacteria for controlling of pollution and offer clue to prevent its entry in the food chain. Total 38 nucleotides and 36 proteins sequences of linA and linB were used for constructing the phylogeny. In addition, analysis on culture dependent and culture independent bacteria were done, which might play a vital role in the degradation of the non-degradable compounds. These bacteria possibly will facilitate in the safety of soil pollution, improving fertility of the soil and prevent entry of HCH in the food chain. Keywords: Hexachlorocyclohexane, linA, linB, homologous, degradation, Table of Contents Abstract Introduction Material And Methods Results And Discussion References Introduction Xenobiotics are chemicals, which did not exist in nature. These are synthetic compounds viz. pesticides, fungicides, herbicides, [...]

The avian influenza is an important infectious disease of birds. Its genome consists of negative sense single stranded segmented RNA which encodes 8 structural proteins (HA, NA, PB1, PB2, PA, M1, M2, NP). The most significant surface proteins of influenza A virus subtype H5N1 are hemagglutinin and neuraminidase for pathogenicity in birds to human. The neighbor-joining method with jukes and cantor algorithm was used for predicting the thirty-six hemagglutinin and thirty-seven neuraminidase nucleotide sequences that were used. The phylogenetic analysis with nucleotide sequences showed proximity between different sources of virus in the same country. It was observed that distribution of almost analogous influenza virus infecting different animals in same country. Therefore, the genome of virus encoded the eight structural proteins, which is important for propagation and infection in the host. We have predicted the sub cellular localization of all proteins in the virus targeting the host. These proteins were located in the plasma membrane and host nucleus interacts with DNA. We have also identified the nine motifs viz. N-glycosylation site, N- myristoylation site, protein kinase C phosphrylation site, casein kinase 2 phosphorylation site, cAMP and cGMP dependent protein kinase phosphorylation site, amidation, cell attachment sequences (RGD), tyrosine kinase, and prokaryotic membrane lipoprotein lipid attachment site in the proteins. These motifs were involved in regulation, activity and stability of virus. This computational study may be easy to understand the proteome function useful for targeting the antiviral drugs against these motifs. Keywords: Avian influenza, hemagglutinin, motifs, neuraminidase, phylogenetic tree, subcellular localization, Table of Contents Abstract Introduction Material And Methods Results And Discussion References Introduction Avian influenza is an important infectious disease of birds ranged from mild to severe form of illness, [...]

Vibrio cholerae have evolved mechanism to become pathogenic to humans with a potential to cause the severe life-threatening diarrhea disease, cholera. Cholera can emerge as explosive outbreaks in the human population. V. cholerae illness is produced primarily through the expression of a potent toxin within the human intestine. Several proteins are involved in the pathogenesis and regulation of bacterial cell activity. The insilico prediction of protein subcellular localization was used to distinguish the actual location in the cells. Total 52 V. cholerae proteins were analyzed with the help of PSLPred. The subcellular localization of these proteins was five in the cells like cytoplasm, periplasm, inner membrane, outer membrane and extracellular space. They have widespread applications in function of proteins in the host cell and in designing the drugs. Keywords: Vibrio cholerae, Cholera, pathogenesis, subcellular localization, drugs, Table of Contents Abstract Introduction Materials And Methods Results And Discussion References Introduction Worldwide 1.3 billion cases of acute diarrhea occur in children below 5 years annually of which more [...]

Dengue has reemerged significantly from the past two decades for the public health problems. Clinicians require a diagnostic test with high sensitivity, which is applicable during early symptomatic phase. PCR is a specific and sensitive molecular technique to detect the gene for monitoring possible Dengue outbreaks and circulating viral serotypes. Bioinformatics tools were used to design and verify the novel Dengue subtype specific primers. In this investigation, 24 primers targeting the structural region of four variants of dengue virus were designed through in silico. There is no cross reactivity found with the primers designed with any other virus. All these sets of primers of dengue were highly specific and may perhaps be helpful for the molecular diagnostic of Dengue viruses. Keywords: Dengue, primers, structural region, Table of Contents Abstract Introduction Material And Methods Results And Discussion References Introduction Dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are a major public health [...]

There is a constant need for assessment of potential allergenic and their patterns of cross-reactivity of genetically modified food (GMF) and pharmaceutical; in which novel proteins are introduced into the human food chain. The aspect for its identification is still in its nascent stage, which includes detection of motifs commonly, occurred in many allergens but rare in ordinary proteins. Transgenic proteins were used by GMF are evaluated on the basis of potential allergenic properties, identification of short identical amino acid sequences were detected from transgenic proteins In this study, bioinformatics approach had been used to detect the potential allergens motifs in amino acid sequences. The purpose of the analysis is to suggest a guideline for food safety, which will aid in human welfare and thereby, controlling the extra use of allergen based transgene introduced into the transgenic foods. Therefore, computationally predicted IgE epitopes from GMF allergen might be an ideal peptide-based novel candidate for immunotherapy. Keywords: Allergens, Epitopes, IgE Genetically modified foods, Motifs, Table of Contents Abstract Introduction Materials And Methods Results And Discussion References Introduction In most nations assessment before authorities is required for the safety of genetically engineered foods prior to [...]

Table of Contents Abstract Introduction Materials And Methods Results And Discussion References Abstract Mycobacterium tuberculosis is a facultative intracellular pathogen that has evolved the ability to survive and multiply within [...]

The utilization of medicinal plants for their therapeutic properties has long been a key component of Indian culture. Unique medicinal characteristics can be found in the phytochemicals that are extracted from these plants. Globally, tuberculosis (TB) burden and management are challenged due to the emergence of new resistant strains of Mycobacterium tuberculosis(Mtb). This highlights the importance of new drug molecules from diverse sources as well as their innovative management options. In this context, the present study formulated an Anti Mtb medicinal plant database (AMMPDB Ver. 1.1), a manually curated database of native Indian medicinal plants that reported anti-tubercular (anti-TB) activities and their potential therapeutic phytochemicals. This is the first-ever freely accessible digital repository. The current version of the database provides users, with information regarding 118 native Indian anti-tubercular medicinal plants and their 3374 phytochemicals. The database provides the following information: Taxonomical ID, botanical description, vernacular names, conservation status, geographical distribution maps, IC-50 value, phytochemical details which include - name, Compound ID, Synonyms, location in plant part, 2D, 3D structures (as per the availability), and their medicinal uses reported in the literature. The tools section of the database is equipped with sequentially catalogued and hyperlinked open-access tools utilized for computational drug designing. A case study has been incorporated under the contributors section to validate the tools section and the phytochemicals of the database. AMMPDB Ver 1.1 will be serviceable to research in computational drug designing and discovery with effectiveness and ease.

Expansion of polyglutamine (CAG) triplets within the coding gene ataxin 2results in transcriptional repression, forming the molecular basis of the neurodegenerative disorder named spinocerebellar ataxia type-2 (SCA2). HDAC inhibitors (HDACi) have been elements of great interest in polyglutamine disorders such as Huntington’s and Ataxia’s. In this study, we have selected hydroxamic acid derivatives as HDACi and performed fragment-based G-QSAR, molecular docking studies and molecular dynamics simulations for elucidating the dynamic mode of action of HDACi with His-Asp catalytic dyad of HDAC4. The model was statistically validated to establish its predictive robustness. The model was statistically significant with r2value of .6297, cross-validated co-relation coefficient q2value of .5905 and pred_r2(predicted square co-relation coefficient) value of .85. An F-test value of 56.11 confirms absolute robustness of the model. Two combinatorial libraries comprising of 3180 compounds were created with hydroxamate moiety as the template and their pIC50activities were predicted based on the G-QSAR model. The combinatorial library created was screened on the basis of predicted activity (pIC50), with two resultant top scoring compounds, HIC and DHC. The interaction of the compounds with His-Asp dyad in terms of H-bond interactions with His802, Asp840, Pro942, and Gly975 residues of HDAC4 was evaluated by docking and 20 ns long molecular dynamics simulations. This study provides valuable leads for structural substitutions required for hydroxamate moiety to exhibit enhanced inhibitory activity against HDAC4. The reported compounds demonstrated good binding and thus can be considered as potent therapeutic leads against ataxia.

With the availability of complete genome sequences of many cyanobacterial species, it is becoming feasible to study the broad prospective of the environmental adaptation and the overall changes at transcriptional and translational level in these organisms. In the evolutionary phase, niche-specific competitive forces have resulted in specific features of the cyanobacterial genomes. In this study, functional composition of the 84 different cyanobacterial genomes and their adaptations to different environments was examined by identifying the genomic composition for specific cellular processes, which reflect their genomic functional profile and ecological adaptation. It was identified that among cyanobacterial genomes, metabolic genes have major share over other categories and differentiation of genomic functional profile was observed for the species inhabiting different habitats. The cyanobacteria of freshwater and other habitats accumulate large number of poorly characterized genes. Strain specific functions were also reported in many cyanobacterial members, of which an important feature was the occurrence of phage-related sequences. From this study, it can be speculated that habitat is one of the major factors in giving the shape of functional composition of cyanobacterial genomes towards their ecological adaptations.

A computational approach for identifying functionally relevant SNPs in gene LIG1 has been proposed. LIG1 is a crucial gene which is involved in excision repair pathways and mutations in this gene may lead to increase sensitivity towards DNA damaging agents. A total of 792 SNPs were reported to be associated with gene LIG1 in dbSNP. Different web server namely SIFT, PolyPhen, CUPSAT, FASTSNP, MAPPER and dbSMR were used to identify potentially functional SNPs in gene LIG1. SIFT, PolyPhen and CUPSAT servers predicted eleven nsSNPs to be intolerant, thirteen nsSNP to be damaging and two nsSNPs have the potential to destabilize protein structure. The nsSNP rs11666150 was predicted to be damaging by all three servers and its mutant structure showed significant increase in overall energy. FASTSNP predicted twenty SNPs to be present in splicing modifier binding sites while rSNP module from MAPPER server predicted nine SNPs to influence the binding of transcription factors. The results from the study may provide vital clues in establishing affect of polymorphism on phenotype and in elucidating drug response.

A large number of influenza A virus outbreaks and mortality occurred in the world recently, an urgent attention to develop effective and sufficient quantity of vaccines are needed. Vaccines are generally protein with immunogenic properties and are not expressed in sufficient quantity because of the codon bias, so it is necessary to optimize its codon in the expression host. Codon optimization was used to improve the protein expression in living organisms by increasing the translational efficiency of gene of interest. Two surface antigenic glycoproteins, hemagglutinin (HA) and neuraminidase (NA) are present in influenza A viruses. We have used HA and NA genes from 19 strains of influenza A viruses for codon optimization in E. coli. Both genes of the influenza virus show that the codon adaptation index (CAI) and GC content of the genes in optimized DNA were enhanced significantly (p<0.01) as compared to wild type. CAI and GC of HA in optimized DNA was enhanced by 3.2 (68.5%) and 1.2 (16.2%) fold respectively, while in NA it was increased by 3.3 (69.7%) and 1.2 (15.8%) fold respectively. Our finding demonstrates that the optimized genes could be useful for better expression in host without any truncated proteins and also helpful for protein folding and function. This work provides new insight in the synthetic biology research.

DNA ligase is an important enzyme and it plays vital role in the replication and repair; also catalyzes nick joining between adjacent bases of DNA. The NAD dependent DNA ligase is selectively present in eubacteria and few viruses; but missing in humans. Homology modeling was used to generate 3-D structure of NAD dependent DNA ligase (LigA) of Mycobacterium tuberculosis using the known template (PDB: 2OWO). Furthermore, the stereochemical quality and torsion angle of 3-D structure was validated. Numerous effective drugs were selected and the active amino acid residue in LigA was targeted and virtual screening through molecular docking was done. In this analysis, four drugs Chloroquine, Hydroxychloroquine, Putrienscine and Adriamycin were found more potent in inhibition of M. tuberculosis through the robust binding affinity between protein-drug interactions in comparison with the other studied drugs. A phylogenetic tree was constructed and it was observed that homology of LigA in M. tuberculosis resembled with other Mycobacterium species. The conserved active amino acids of LigA may be useful to target these drugs. These findings could be used as the starting point of a rational design of novel antibacterial drugs and its analogs.

Abstract: The genus flavivirus in the family Flaviviridae consists of many arthropod transmitted human pathogens. siRNA is a novel strategy used for controlling the gene expression of flavivirus. These are 20–25 nucleotide long dsRNA molecules that target genes at expression level. Nine flavivirus genomes were used to in silico identify the siRNA. Twenty three siRNAs were identified in the 5′ UTR and capsid protein encoding gene from flavivirus. These siRNA can be useful to knockdown the flavivirus and it might also be helpful for constructing live attenuated vaccine.

Peptide deformylase (PDF) is a ubiquitous bacterial metalloenzyme responsible to cleave the formyl group from nascent polypeptides, supporting in the maturation. It plays a vital role in the survival of bacterial cells which is conserved in the eubacteria and is considered to be an attractive target for developing new antibacterial agents. Homology modeling was employed for generation of 3-D structure of PDF of M. tuberculosis H37Rv and showed 92.5 amino acid in the allowed region of Ramachandran plot. PDF was used as target for a set of inhibitors with substantial structural differences. Docking results show that the BB-3497, BBS-54, Actinonin and BBS-02 bind with high affinity to enzyme active site. Phylogeny of PDF in M. tuberculosis H37Rv shows homology with other strains of pathogenic bacteria. These data validate PDF as a novel target for the design of a new generation of antimycobacterial agents.

Abstract: Homology modeling of NS3 helicase in Tick-borne encephalitis virus using known protein crystal structure was done. Its 3-D structure was evaluated and validated using PROCHECK comprising amino acid residues in favored region of Ramachandran plot. Helicase forms a large family of proteins which ubiquitously distributes in wide variety of organisms. It plays crucial role in transcription and replication of single-stranded viral RNA genomes. Consequently, NS3 represents an interesting target for the development of specific antiviral inhibitors. Several helicase inhibiting effective drugs and analogs were selected and the active amino acid residues were targeted. Levovirin, Ribamidine and Ribavirin were found more potent to inhibit TBEV on the basis of robust binding affinity between protein-drug interactions. This finding may help to understand the nature of helicase and development of specific anti-TBEV therapies.

Parkinson's disease (PD) is a neurodegenerative disorder of central nervous system (CNS) that impaired the patient motor skills, speech and other functions. Adenosine A2A receptors have a unique cellular distribution in the neuron, which is used as a potential target for PD. Homology modeling was used to construct the 3-D structure of A2A using the known template (PDB: 2VT4), and the stereochemical quality was validated. Several effective antagonist drugs were selected and active amino acid residues in A2A were targeted on the basis of robust binding affinity between proteindrug interactions in molecular docking. Six antagonists, Bromocriptine, Cabergoline, Etilevodopa, Lysuride, Melevodopa and Pramipexole, were found more potent for binding and the active amino acids residues were identified (http://www.rcsb.org/pdb/) in A2A receptor. It could be used as the basis for rationale designing of novel antagonist drugs against Parkinson's diseas.

Aerolysin (Aer) is a pore forming toxin that plays important role in pathogenesis of Aeromonas hydrophila which causes hemorrhagic septicemia in aquatic and terrestrial animals including humans. Aerolysin aggregates in the forms of oligomers on the surface of animal RBCs and its ability to bind with Glycosylphosphatidyl inositol (GPI) anchored protein receptor. The primers were designed for Aer gene and amplified to target the complete ORF of Aeromonas hydrophila; later it was sequenced. Homology modeling was used to construct the 3-D structure of Aer using known template (PDB: 1PRE) and the stereochemical quality, torsion angle of 3-D structure was validated. Several drugs were used for virtual screening through molecular docking and four drugs viz. Aralia, Gypsogenin, Saponin and TS-saponin are more potent for inhibition of oligomerization of aer through robust binding affinity between protein-drug interactions. The phylogenetic analysis showed that homology of Aer present in A. hydrophila resembled with other bacteria. The findings could help as a beginning in rationale designing of novel drugs and its analogs.

This study examines the effect of epigallocatechin gallate (EGCG) on signaling pathways, epigenetic modulators and tumour suppressor genes in cervical cancer cells, HeLa. qRT-PCR, ELISA-based enzymatic assays and in silico studies were used to catalogue the modulation of these genes by EGCG treatment. qRT-PCR showed transcriptional modulation of several epigenetic modifiers including DNA methyltransferases and histone modifiers (DNMT1, DNMT3B, DNMT3A, AURKA, AURKC, AURKB, KDM4A, KDM5C, PRMT7, PRMT6, UBE2B, HDAC5, HDAC6, HDAC7 and HDAC11. Furthermore, ELISA-based assays showed that EGCG lowered the activity of DNA methyltransferases, histone deacetylases and histone methyltransferases (H3K9). Molecular docking results suggests that EGCG may competitively inhibit some epigenetic enzymes (DNMT1, DNMT3A, HDAC2, HDAC3, HDAC4, HDAC7 and EZH2). A functional outcome of these epigenetic alterations could be inferred from the reversal of promoter hypermethylation of tumour suppressor genes by quantitative methylation array and transcriptional re-expression of tumour suppressor genes including TP73, PTEN, SOCS1, CDH1, RARβ,and DAPK1by qRT-PCR. Downregulation of key signaling moieties of PI3K, Wnt and MAPK pathways, cell cycle regulators, metastasis regulators and pro-inflammatory moieties including TERT, CCNB1, CCNB2, MMP2, MMP7. PIK3C2B, PIK3CA, MAPK8and IL6was also observed. In silico protein–protein interaction network analysis followed by KEGG analysis discerned the active participation of gene sets towards cancer pathways. This study comprehensively explains EGCG’s anti-cancer mechanism via the synchronized transcriptional alteration of several molecular targets across different signaling pathways and reversal of tumour suppressor gene silencing through modulation of epigenetic enzymes.

The rapid onset of resistance to new drugs and emergence of antibiotic resistant bacteria has led to resurgence in life-threatening bacterial infections. These problems have revitalized interest in antibiotics and lead to new research. To gain further insight between structural and biological activity of Clostridium perfringens,a gram-positive anaerobe responsible for food poisoning, mynecrosis in wound infections, and enterotoxemia in humans. We have considered various in silicoapproaches for developing new drug leads, based on small ligand structure. The importance of neuraminidases in the virulence of C. perfringensmakes it a potent target for the studies of drug designing against this microbe. Natural products or their direct derivatives play crucial roles in many diseases. In the present study, 3D QSAR analysis using kNN-MFA method was performed on a series of pterocarpan derivatives as Clostridial neuraminidase inhibitors. Twenty-five compounds using random selection and sphere exclusion method for the division of dataset into training and test set were chosen. kNN-MFA methodology with stepwise, simulated annealing and genetic algorithm was used for model building and four predictive models have been generated. The most significant model has a high internal predictivity of 64.80% (q2 = 0.6480) and an external predictivity of 95.46% (r2 = 0.9546). Model showed that electrostatic and steric interactions play important role in determining neuraminidase inhibitory activity. The kNN-MFA plots provide further understanding of the relationship between structural features of substituted pterocarpan derivatives and their activities which were applied for designing new compounds as inhibitors. The drug likeliness of these compounds was checked through ADME property prediction and their interaction with the neuraminidase was checked by molecular docking studies. Moreover, analysis of protein–protein interaction network of NanI in C. perfringenswas done.