Dr. Parth Sarthi Sen Gupta
@dypiu.ac.in
Assistant Professor
D Y Patil International University
Dr. Parth Sarthi Sen Gupta is an Assistant professor in School of Biosciences and Bioengineering, D Y Patil International University. He has published more than 40 research articles and book chapter in reputed peer reviewed Journals. He is a Computational Biologist working in designing and development of therapeutics against various diseases. His research work on COVID19 has been highlighted by various national and international news agencies and recognized by World health organizations.
EDUCATION
Experience
2022 - Present
Assistant Professor (Senior Grade)
School of Bioengineering and Biological Sciences
D Y PATIL INTERNATIONAL UNIVERSITY,Pune
2018 - 2022
Post-Doctoral Research Scientist
Department of Chemical Sciences
Indian Institute of Science Education and Research, Berhampur,Ganjam
RESEARCH, TEACHING, or OTHER INTERESTS
Multidisciplinary, Biotechnology, Biochemistry, Genetics and Molecular Biology, Immunology and Microbiology
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Satyaranjan Biswal, Parth Sarthi Sen Gupta, Saroj Kumar Panda, Haamid Rasool Bhat, and Malay Kumar Rana
Springer Science and Business Media LLC
Parth Sarthi Sen Gupta, Saroj Kumar Panda, Abhijit Kumar Nayak, and Malay Kumar Rana
American Chemical Society (ACS)
The spread of the monkeypox virus has surged during the unchecked COVID-19 epidemic. The most crucial target is the viral envelope protein, p37. However, lacking p37's crystal structure is a significant hurdle to rapid therapeutic discovery and mechanism elucidation. Structural modeling and molecular dynamics (MD) of the enzyme with inhibitors reveal a cryptic pocket occluded in the unbound structure. For the first time, the inhibitor's dynamic flip from the active to the cryptic site enlightens p37's allosteric site, which squeezes the active site, impairing its function. A large force is needed for inhibitor dissociation from the allosteric site, ushering in its biological importance. In addition, hot spot residues identified at both locations and discovered drugs more potent than tecovirimat may enable even more robust inhibitor designs against p37 and accelerate the development of monkeypox therapies.
Somrita Padma, Ritwik Patra, Parth Sarthi Sen Gupta, Saroj Kumar Panda, Malay Kumar Rana, and Suprabhat Mukherjee
MDPI AG
Colorectal cancer (CRC) is one of the most common cancers and is the second-highest in cancer-related deaths worldwide. The changes in gut homeostasis and microbial dysbiosis lead to the initiation of the tumorigenesis process. Several pathogenic gram-negative bacteria including Fusobacterium nucleatum are the principal contributors to the induction and pathogenesis of CRC. Thus, inhibiting the growth and survival of these pathogens can be a useful intervention strategy. Fibroblast activation protein-2 (Fap2) is an essential membrane protein of F. nucleatum that promotes the adherence of the bacterium to the colon cells, recruitment of immune cells, and induction of tumorigenesis. The present study depicts the design of an in silico vaccine candidate comprising the B-cell and T-cell epitopes of Fap2 for improving cell-mediated and humoral immune responses against CRC. Notably, this vaccine participates in significant protein–protein interactions with human Toll-like receptors, especially with TLR6 reveals, which is most likely to be correlated with its efficacy in eliciting potential immune responses. The immunogenic trait of the designed vaccine was verified by immune simulation approach. The cDNA of the vaccine construct was cloned in silico within the expression vector pET30ax for protein expression. Collectively, the proposed vaccine construct may serve as a promising therapeutic in intervening F. nucleatum-induced human CRC.
Nabarun Chandra Das, Parth Sarthi Sen Gupta, Saroj Kumar Panda, Malay Kumar Rana, and Suprabhat Mukherjee
Elsevier BV
Saroj Kumar Panda, Parth Sarthi Sen Gupta, and Malay Kumar Rana
Wiley
AbstractSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has continued evolving for survival and adaptation by mutating itself into different variants of concern, including omicron. Several studies and clinical trials found fluvoxamine, an Food and Drug Administration‐approved antidepressant drug, to be effective at preventing mild coronavirus disease 2019 (COVID‐19) from progressing to severe diseases. However, the mechanism of fluvoxamine's direct antiviral action against COVID‐19 is still unknown. Fluvoxamine was docked with 11 SARS‐CoV‐2 targets and subjected to stability, conformational changes, and binding free energy analyses to explore its mode of action. Of the targets, nonstructural protein 14 (NSP14), main protease (Mpro), and papain‐like protease (PLpro) had the best docking scores with fluvoxamine. Consistent with the docking results, it was confirmed by molecular dynamics simulations that the NSP14 N7‐MTase ((N7‐guanine)‐methyltransferase)–fluvoxamine, Mpro–fluvoxamine, and PLpro–fluvoxamine complexes are stable, with the lowest binding free energies of −105.1, −82.7, and − 38.5 kJ/mol, respectively. A number of hotspot residues involved in the interaction were also identified. These include Glu166, Asp187, His41, and Cys145 in Mpro, Gly163 and Arg166 in PLpro, and Glu302, Gly333, and Phe426 in NSP14, which could aid in the development of better antivirals against SARS‐CoV‐2.
Madhu Yadav, Ritika Srivastava, Farha Naaz, Parth Sarthi Sen Gupta, Saroj Kumar Panda, Malay Kumar Rana, and Ramendra K. Singh
Informa UK Limited
Abstract To improve rationally the efficacy of the non-nucleoside human immunodeficiency virus (HIV-1) inhibitors, it is important to have a precise and detailed understanding of the HIV-1 reverse transcriptase (RT) and inhibitor interactions. For the 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio) thymine (HEPT) type of nucleoside reverse transcriptase inhibitors (NNRTIs), the H-bond between the N-3H of the inhibitor and the backbone carbonyl group of K101 represents the major hydrophilic interaction. This H-bond contributes to the NNRTI binding affinity. The descriptor analyses of different uracil derivatives proved their good cell internalization. The bioactivity score reflected higher drug likeness score and the ligands showed interesting docking results. All molecules were deeply buried and stabilized into the allosteric site of HIV-1 RT. For majority of molecules, residues Lys101, Lys103, Tyr181 and Tyr188 were identified as key protein residues responsible for generation of H-bond and major interactions were similar to all known NNRTIs while very few molecules interacted with residues Phe227 and Tyr318. The TOPKAT protocol available in Discovery Studio 3.0 was used to predict the pharmacokinetics of the designed uracil derivatives in the human body. The molecular dynamics (MD) and post-MD analyses results reflected that the complex HIVRT:5 appeared to be more stable than the complex HIVRT:HEPT, where HEPT was used as reference. Different uracil derivatives have been synthesized by using uracil as starting material and commercially available propargyl bromide. The N-1 derivative of uracil was further reacted with sodamide and different aldehydes/ketones bearing alkyl and phenyl ring to obtain hydroxyalkynyl uracil derivatives as NNRTIs. Communicated by Ramaswamy H. Sarma
Uddipan Bhattacharya, Saroj Kumar Panda, Parth Sarthi Sen Gupta, and Malay Kumar Rana
Elsevier BV
Abhigyan Choudhury, Parth Sarthi Sen Gupta, Saroj Kumar Panda, Malay Kumar Rana, and Suprabhat Mukherjee
Elsevier BV
Sampa Gorai, Nabarun Chandra Das, Parth Sarthi Sen Gupta, Saroj Kumar Panda, Malay Kumar Rana, and Suprabhat Mukherjee
Elsevier BV
Abhik Kumar Ray, Parth Sarthi Sen Gupta, Saroj Kumar Panda, Satyaranjan Biswal, Uddipan Bhattacharya, and Malay Kumar Rana
Elsevier BV
Pritha Chakraborty, Parth Sarthi Sen Gupta, Shankar Dey, Nabarun Chandra Das, Ritwik Patra, and Suprabhat Mukherjee
Elsevier
Nabarun Chandra Das, Parth Sarthi Sen Gupta, Satyaranjan Biswal, Ritwik Patra, Malay Kumar Rana, and Suprabhat Mukherjee
Informa UK Limited
Abstract Cystatin is a small molecular weight immunomodulatory protein of filarial parasite that plays a pivotal role in downregulating the host immune response to prolong the survival of the parasite inside the host body. Hitherto, this protein is familiar as an inhibitor of human proteases. However, growing evidences on the role of cystatin in regulating inflammatory homeostasis prompted us to investigate the molecular reasons behind the explicit anti-inflammatory trait of this protein. We have explored molecular docking and molecular dynamics simulation approaches to explore the interaction of cystatin of Wuchereria bancrofti (causative parasite of human filariasis) with human Toll-like receptors (TLRs). TLRs are the most crucial component of frontline host defence against pathogenic infections including filarial infection. Our in-silico data clearly revealed that cystatin strongly interacts with the extracellular domain of TLR4 (binding energy=-93.5 ± 10 kJ/mol) and this biophysical interaction is mediated by hydrogen bonding and hydrophobic interaction. Molecular dynamics simulation analysis revealed excellent stability of the cystatin-TLR4 complex. Taken together, our data indicated that cystatin appears to be a ligand of TLR4 and we hypothesize that cystatin-TLR4 interaction most likely to play a key role in activating the alternative activation pathways to establish an anti-inflammatory milieu. Thus, the study provokes the development of chemotherapeutics and/or vaccines for targeting the cystatin-TLR4 interaction to disrupt the pathological attributes of human lymphatic filariasis. Our findings are expected to provide a novel dimension to the existing knowledge on filarial immunopathogenesis and it will encourage the scientific communities for experimental validation of the present investigation. Communicated by Ramaswamy H. Sarma
Parth Sarthi Sen Gupta, Satyaranjan Biswal, Saroj Kumar Panda, Abhik Kumar Ray, and Malay Kumar Rana
Informa UK Limited
Abstract While an FDA approved drug Ivermectin was reported to dramatically reduce the cell line of SARS-CoV-2 by ∼5000 folds within 48 h, the precise mechanism of action and the COVID-19 molecular target involved in interaction with this in-vitro effective drug are unknown yet. Among 12 different COVID-19 targets along with Importin-α studied here, the RNA dependent RNA polymerase (RdRp) with RNA and Helicase NCB site show the strongest affinity to Ivermectin amounting −10.4 kcal/mol and −9.6 kcal/mol, respectively, followed by Importin-α with −9.0 kcal/mol. Molecular dynamics of corresponding protein-drug complexes reveals that the drug bound state of RdRp with RNA has better structural stability than the Helicase NCB site and Importin-α, with MM/PBSA free energy of −187.3 kJ/mol, almost twice that of Helicase (−94.6 kJ/mol) and even lower than that of Importin-α (−156.7 kJ/mol). The selectivity of Ivermectin to RdRp is triggered by a cooperative interaction of RNA-RdRp by ternary complex formation. Identification of the target and its interaction profile with Ivermectin can lead to more powerful drug designs for COVID-19 and experimental exploration. Graphical Abstract Communicated by Ramaswamy H. Sarma
Sahini Banerjee, Parth Sarthi Sen Gupta, Rifat Nawaz Ul Islam, and Amal Kumar Bandyopadhyay
Springer Science and Business Media LLC
AbstractSalt-bridges play a key role in the thermostability of proteins adapted in stress environments whose intrinsic basis remains to be understood. We find that the higher hydrophilicity of PfP than that of HuP is due to the charged but not the polar residues. The primary role of these residues is to enhance the salt-bridges and their ME. Unlike HuP, PfP has made many changes in its intrinsic property to strengthen the salt-bridge. First, the desolvation energy is reduced by directing the salt-bridge towards the surface. Second, it has made bridge-energy more favorable by recruiting energetically advantageous partners with high helix-propensity among the six possible salt-bridge pairs. Third, ME-residues that perform intricate interactions have increased their energy contribution by making major changes in their binary properties. The use of salt-bridge partners as ME-residues, and ME-residues' overlapping usage, predominant in helices, and energetically favorable substitution are some of the favorable features of PfP compared to HuP. These changes in PfP reduce the unfavorable, increase the favorable ME-energy. Thus, the per salt-bridge stability of PfP is greater than that of HuP. Further, unfavorable target ME-residues can be identified whose mutation can increase the stability of salt-bridge. The study applies to other similar systems.
Saroj Kumar Panda, Shalini Saxena, Parth Sarthi Sen Gupta, and Malay Kumar Rana
Elsevier BV
Saroj Kumar Panda, Parth Sarthi Sen Gupta, Satyaranjan Biswal, Abhik Kumar Ray, and Malay Kumar Rana
American Chemical Society (ACS)
SARS-CoV-2, a novel coronavirus causing overwhelming death and infection worldwide, has emerged as a pandemic. Compared to its predecessor SARS-CoV, SARS-CoV-2 is more infective for being highly contagious and exhibiting tighter binding with host angiotensin-converting enzyme 2 (hACE-2). The entry of the virus into host cells is mediated by the interaction of its spike protein with hACE-2. Thus, a peptide that has a resemblance to hACE-2 but can overpower the spike protein–hACE-2 interaction will be a potential therapeutic to contain this virus. The non-interacting residues in the receptor-binding domain of hACE-2 have been mutated to generate a library of 136 new peptides. Out of this library, docking and virtual screening discover seven peptides that can exert a stronger interaction with the spike protein than hACE-2. A peptide derived from simultaneous mutation of all the non-interacting residues of hACE-2 yields almost three-fold stronger interaction than hACE-2 and thus turns out here to be the best peptide inhibitor of the novel coronavirus. The binding of the best peptide inhibitor with the spike protein is explored further by molecular dynamics, free energy, and principal component analysis, which demonstrate its efficacy compared to hACE-2. The delivery of the screened inhibitors with nanocarriers like metal–organic frameworks will be worthy of further consideration to boost their efficacy.
Nabarun Chandra Das, Ritwik Patra, Parth Sarthi Sen Gupta, Pratik Ghosh, Manojit Bhattacharya, Malay Kumar Rana, and Suprabhat Mukherjee
Elsevier BV
Parth Sarthi Sen Gupta, Satyaranjan Biswal, Dipankar Singha, and Malay Kumar Rana
Informa UK Limited
Abstract Communicated by Ramaswamy H. Sarma
Vishal K. Singh, Ritika Srivastava, Parth Sarthi Sen Gupta, Farha Naaz, Himani Chaurasia, Richa Mishra, Malay Kumar Rana, and Ramendra K. Singh
Informa UK Limited
Abstract In view of the low toxicity of NNRTIs in comparison to NRTIs, a new series of diarylpyrimidine derivatives has been designed as NNRTIs against HIV-1. In silico studies using DS 3.0 software have shown that these compounds behaved as NNRTIs while interacting at the allosteric site of HIV-RT. The designed compounds have shown promising docking results, which revealed that all compounds formed hydrogen bonds with Lys101, Lys103, Tyr181, Tyr318 and π- interactions with Tyr181, Tyr188, Phe227 and Trp229 amino acid residues located in the non-nucleoside inhibitor binding pocket (NNIBP) of HIV-RT protein. The intended molecules have shown high binding affinity with HIV-1 RT, analogous to standard drug molecule—etravirine. TOPKAT results confirmed that the designed compounds were found to be less toxic than the reference drug. Further, employing molecular dynamics simulations, the complexes of the best screened compound 6 and etravirine with the HIV-1 RT protein were analyzed by calculating the RMSD, RMSF, R g, number of hydrogen bonds, principal components of the coordinates, molecular mechanics-Poisson-Boltzmann surface area-based binding free energy and their decomposition for different interactions. The analysis demonstrated the higher stability of compound 6 than the standard drug etravirine with HIV-1 RT. The interactions like hydrogen-bonding, van-der-Waals, electrostatic and the solvent accessible surface energy have favorable contributions to the complex stability. Thus, the shortlisted designed compound has great promise as a potential inhibitor against HIV-1 RT. Graphical Abstract Highlights New diarylpyrimidine derivatives have been designed as potential anti-HIV agents. The compounds were docked at the allosteric site of HIV-RT protein (PDB ID: 3MEC) to study the stability of protein-ligand complex. Docking studies indicated the stable ligand-protein complexes of all designed compounds. The TOPKAT protocol in DS 3.0 software was used to evaluate the toxicity of the designed diarylpyrimidine derivatives. Molecular Dynamics studies were performed on best screened compound. Communicated by Ramaswamy H. Sarma
Parth Sarthi Sen Gupta, Haamid Rasool Bhat, Satyaranjan Biswal, and Malay Kumar Rana
Elsevier BV
Ritika Srivastava, Sunil K. Gupta, Farha Naaz, Parth Sarthi Sen Gupta, Madhu Yadav, Vishal Kumar Singh, Anuradha Singh, Malay Kumar Rana, Satish Kumar Gupta, Dominique Schols,et al.
Elsevier BV
Parth Sarthi Sen Gupta and Malay Kumar Rana
American Chemical Society (ACS)
At times, combination therapy has proven to be very effective. While no cure is available to date, herein we put forward with rationale and supporting evidence that if administrated simultaneously, a combination of FDA-approved drugs comprising ivermectin, famotidine, and doxycycline may provide robust chemoprophylaxis effective against COVID-19.
Parth Sarthi Sen Gupta, Rifat Nawaz UI Islam, Sahini Banerjee, Arnab Nayek, Malay Kumar Rana, and Amal Kumar Bandyopadhyay
Informa UK Limited
Abstract Alkaptonuria (AKU) is an autosomal recessive disorder, which is caused by a site-specific mutation(s) and thus, impaired the function of Homogentisate-1, 2-dioxygenase (HGD), an essential enzyme for the catabolism of phenylalanine and tyrosine. Among frameshift, intronic, splice-site and missense mutations, the latter has been the most common form of genetic variations for the disease. How do the acquired mutations in HGD correlate with the disease? Systematic staged-screening of some sixty-five mutations, which are known to have a relation with the disease, by GVGD, SIFT, SNAP, PANTHER, SDM, PHD-SNP, Meta-SNP, Pmut and Mutpred methods, showed that mutations, W60G, A122D and V300G are potentially related with the severity of AKU. Detailed analyses on molecular docking and molecular dynamics simulation (MDS) of these mutants against the wild-type HGD reveal the loss of structural and molecular dynamic properties of the enzyme. Further, the observed conformational flexibility in mutants at targeted peptide segments seems to have a relation with the impairment of the function of HGD. Taken together, the study involves a designed computational methodology to analyse the disease-associated nsSNPs for AKU, the knowledge of which seems to have potential applications in drug therapies for the disease in particular and other similar systems in general. Communicated by Ramaswamy H. Sarma
Haamid Rasool Bhat, Parth Sarthi Sen Gupta, Satyaranjan Biswal, and Malay Kumar Rana
American Chemical Society (ACS)
Analytical methods often involve expensive instrumentation and tedious sample pretreatment for an analyte detection. Being toxic and detrimental to human health, sensing of cyanide (CN–), fluoride (F–), chloride (Cl–), bromide (Br–), nitrate (NO3–), acetate (CH3COO–), and bisulfate (HSO4–) is performed by a boron-based molecular receptor, N,N,N,3,5-pentamethyl-4-{2-thia-9-boratricyclo[8.4.0.03,8]tetradeca-1(10),3(8),4,6,11,13-hexaen-9-yl}anili-nium (1), and the three newly designed receptors from it. Thermodynamics, electronic structure, and photophysical properties are computed by employing density functional theory (DFT) and time-dependent density functional theory (TD-DFT) to explore selective sensing of these anions and its mechanism. Free-energy changes (ΔG) and binding energies (ΔE) suggest that among these anions, only binding of CN– and F– is thermodynamically feasible with a very strong binding affinity with the receptors. Boron atoms containing positive natural charges act as the electrophilic centers to bind the anions involving a 2p–2p orbital overlap resulting in charge transfer. In the receptor–analyte complexes with CN– and F–, fluorescence is quenched due to the intramolecular charge transfer transitions (π–π* transitions in the case of the receptors lead to fluorescence), internal conversion, and associated configurational changes. Among the six tested functionals, CAM-B3LYP/6-31G(d) is found to be the most accurate one. The designed receptors are better fluorescent probes for F– and CN–, demonstrating their importance for the practical utility.
Shyamashree Banerjee, Parth Sarthi Sen Gupta, and Amal Kumar Bandyopadhyay
Springer Science and Business Media LLC