High-throughput virtual screening of small-molecule inhibitors targeting immune cell checkpoints to discover new immunotherapeutics for human diseases

Singh, Satyendra; Kumar, Ketan; Panda, Mamta; Srivastava, Abhishek; Mishra, Amit; Prajapati, Vijay Kumar

doi:10.1007/s11030-022-10452-2

Cited by 19 publications

(9 citation statements)

References 61 publications

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“…[ 55 ] The stability of the complexes was evaluated throughout the simulation trajectory using the five parameters, which include Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Radius of Gyration (Rg), Solvent Accessible Surface Area (SASA), and the number of Hydrogen bonds formation between protein and peptide complexes. [ 56 ]…”

Section: Resultsmentioning

confidence: 99%

An in‐silico‐based study identified peptide inhibitors that can block the egression of the monkeypox virus by inhibiting the p37 protein target

et al. 2023

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Monkeypox is a zoonotic disease caused by the Poxviridiea family virus Monkeypox. According to the Centers for Disease Control and Prevention, 70,420 monkeypox virus infections had been reported in 107 countries as of October 6, 2022. New studies have concluded that the monkeypox outbreak is caused by a strain with a unique mutation, increasing the possibility that the virus may develop resistance to current medicines by accumulating mutations in therapeutic targets. As peptide‐based therapeutics impede the drug target through multiple interactions, it may offer a better therapeutic solution to the possible drug resistance issue related to monkeypox treatment. Therefore, in this work, we screened an antiviral peptide library, the CPP site 2.0 database, against the p37 target protein using molecular docking approaches. The p37 is required for the viral pathogen's successful egression and spread. The allergenicity and physicochemical properties of the peptides were thoroughly analyzed before the molecular docking studies for selecting druggable candidates. The interactions of the peptides bearing the highest docking score were validated further by using molecular dynamics (MD) simulation studies. Our investigation revealed that two cell‐penetrating peptides of the CPP site 2.0 database might effectively prevent the egression and spread of the MPXV by inhibiting p37. Following more testing, these peptides can be explored in developing peptide‐based therapies against the MPX therapy.

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Section: Resultsmentioning

confidence: 99%

An in‐silico‐based study identified peptide inhibitors that can block the egression of the monkeypox virus by inhibiting the p37 protein target

et al. 2023

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“…Next, the topology generation was achieved, which is the foremost step, as this contains all the information related to nonbonded and bonded parameters essential to characterize the docked complex inside a simulation. A Rhombic dodecahedron boundary box in the system was used to mimic the natural environment along with a protein complex, water (solvent; SPC water model), and ions added (Singh 2022 ; Singh and Prajapati 2022 ). Further, the complex was energy minimized to reduce steric clashes and weak interactions.…”

Section: Methodsmentioning

confidence: 99%

“…Later, the system was stabilized with NVT and NPT at 100 ps time frames. Finally, the MD simulation was carried out for 100 ns to calculate RMSD (Root Mean Square Deviation) and RMSF (Root Mean Square Fluctuation) for the protein backbone and side chains, respectively (Singh 2022 ; Singh and Prajapati 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Multi-pathogen based chimeric vaccine to fight against COVID-19 and concomitant coinfections

et al. 2023

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Background COVID-19 has proved to be a fatal disease of the year 2020, due to which thousands of people globally have lost their lives, and still, the infection cases are at a high rate. Experimental studies suggested that SARS-CoV-2 interacts with various microorganisms, and this coinfection is accountable for the augmentation of infection severity. Methods and results In this study, we have designed a multi-pathogen vaccine by involving the immunogenic proteins from S. pneumonia, H. influenza, and M. tuberculosis , as they are dominantly associated with SARS-CoV-2. A total of 8 antigenic protein sequences were selected to predict B-cell, HTL, and CTL epitopes restricted to the most prevalent HLA alleles. The selected epitopes were antigenic, non-allergenic, and non-toxic and were linked with adjuvant and linkers to make the vaccine protein more immunogenic, stable, and flexible. The tertiary structure, Ramachandran plot, and discontinuous B-cell epitopes were predicted. Docking and MD simulation study has shown efficient binding of the chimeric vaccine with the TLR4 receptor. Conclusion The in silico immune simulation analysis has shown a high level of cytokines and IgG after a three-dose injection. Hence, this strategy could be a better way to decrease the disease's severity and could be used as a weapon to prevent this pandemic. Supplementary Information The online version contains supplementary material available at 10.1007/s10529-023-03380-0.

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“…To evaluate the interactions between the AVPs and their prospective molecular targets at the microscopic level, GROMOS96 43a1 force field and the particle mesh Ewald summation method were used to run the MD simulation of the complexes mentioned above [ 57 , 58 ]. For protein topology creation and characterization of bonded and non-bonded regions, the pdb2gmx command was given.…”

Section: Methodsmentioning

confidence: 99%

Identification of multi-targeting natural antiviral peptides to impede SARS-CoV-2 infection

et al. 2022

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SARS-CoV-2 and its variants cause serious health concerns throughout the world. The alarming increase in the daily number of cases has become a nightmare in many low-income countries; although some vaccines are available, their high cost and low vaccine production make them unreachable to ordinary people in developing countries. Other treatment strategies are required for novel therapeutic options. The peptide-based drug is one of the alternatives with low toxicity, more specificity, and ease of synthesis. Herein, we have applied structure-based virtual screening to identify potential peptides targeting the critical proteins of SARS-CoV-2. Non-toxic natural antiviral peptides were selected from the enormous number of peptides. Comparative modeling was applied to prepare a 3D structure of selected peptides. 3D models of the peptides were docked using the ClusPro docking server to determine their binding affinity and peptide-protein interaction. The high-scoring peptides were docked with other crucial proteins to analyze multiple targeting peptides. The two best peptides were subjected to MD simulations to validate the structure stability and evaluated RMSD, RMSF, Rg , SASA, and H-bonding from the trajectory analysis of 100 ns. The proposed lead peptides can be used as a broad-spectrum drug and potentially develop as a therapeutic to combat SARS-CoV-2, positively impacting the current pandemic. Supplementary Information The online version contains supplementary material available at 10.1007/s11224-022-02113-9.

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High-throughput virtual screening of small-molecule inhibitors targeting immune cell checkpoints to discover new immunotherapeutics for human diseases

Cited by 19 publications

References 61 publications

An in‐silico‐based study identified peptide inhibitors that can block the egression of the monkeypox virus by inhibiting the p37 protein target

An in‐silico‐based study identified peptide inhibitors that can block the egression of the monkeypox virus by inhibiting the p37 protein target

Multi-pathogen based chimeric vaccine to fight against COVID-19 and concomitant coinfections

Identification of multi-targeting natural antiviral peptides to impede SARS-CoV-2 infection

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