scholarly journals Enfuvirtide, an HIV-1 fusion inhibitor peptide, can act as a potent SARS-CoV-2 fusion inhibitor: an in silico drug repurposing study

2021 ◽  
pp. 1-11
Author(s):  
Khadijeh Ahmadi ◽  
Alireza Farasat ◽  
Mosayeb Rostamian ◽  
Behrooz Johari ◽  
Hamid Madanchi
Keyword(s):  
In Silico ◽  
Drug Repurposing ◽  
Fusion Inhibitor ◽  
Inhibitor Peptide ◽  
Hiv 1

scholarly journals Lipid Vesicles Loaded with an HIV-1 Fusion Inhibitor Peptide as a Potential Microbicide

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 502 ◽  
Author(s):  
Elena Sánchez-López ◽  
Anna Paús ◽  
Ignacio Pérez-Pomeda ◽  
Ana Calpena ◽  
Isabel Haro ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Polymeric Nanoparticles ◽  
Entrapment Efficiency ◽  
Lipid Vesicles ◽  
Fusion Inhibitor ◽  
Vaginal Mucosa ◽  
Prolonged Release ◽  
Vaginal Tissue ◽  
Inhibitor Peptide ◽  
Hiv 1

The effective use of fusion inhibitor peptides against cervical and colorectal infections requires the development of sustained release formulations. In this work we comparatively study two different formulations based on polymeric nanoparticles and lipid vesicles to propose a suitable delivery nanosystem for releasing an HIV-1 fusion inhibitor peptide in vaginal mucosa. Polymeric nanoparticles of poly-d,l-lactic-co-glycolic acid (PLGA) and lipid large unilamellar vesicles loaded with the inhibitor peptide were prepared. Both formulations showed average sizes and polydispersity index values corresponding to monodisperse systems appropriate for vaginal permeation. High entrapment efficiency of the inhibitor peptide was achieved in lipid vesicles, which was probably due to the peptide’s hydrophobic nature. In addition, both nanocarriers remained stable after two weeks stored at 4 °C. While PLGA nanoparticles (NPs) did not show any delay in peptide release, lipid vesicles demonstrated favorably prolonged release of the peptide. Lipid vesicles were shown to improve the retention of the peptide on ex vivo vaginal tissue in a concentration sufficient to exert its pharmacological effect. Thus, the small size of lipid vesicles, their lipid-based composition as well as their ability to enhance peptide penetration on vaginal tissue led us to consider this formulation as a better nanosystem than polymeric nanoparticles for the sustained delivery of the HIV-1 fusion inhibitor peptide in vaginal tissues.

Potential HIV-1 fusion inhibitors mimicking gp41-specific broadly neutralizing antibody 10E8: In silico discovery and prediction of antiviral potency

2018 ◽  
Vol 16 (02) ◽  
pp. 1840007 ◽  
Author(s):  
Alexander M. Andrianov ◽  
Ivan A. Kashyn ◽  
Alexander V. Tuzikov
Keyword(s):  
In Silico ◽  
Binding Free Energy ◽  
Neutralizing Antibody ◽  
Free Energy Calculations ◽  
Fusion Inhibitor ◽  
Broadly Neutralizing Antibody ◽  
Screening Platform ◽  
Dynamics Simulations ◽  
Hiv 1 ◽  
Inhibitor Scaffolds

An integrated computational approach to in silico drug design was used to identify novel HIV-1 fusion inhibitor scaffolds mimicking broadly neutralizing antibody (bNab) 10E8 targeting the membrane proximal external region (MPER) of the HIV-1 gp41 protein. This computer-based approach included (i) generation of pharmacophore models representing 3D-arrangements of chemical functionalities that make bNAb 10E8 active towards the gp41 MPER segment, (ii) shape and pharmacophore-based identification of the 10E8-mimetic candidates by a web-oriented virtual screening platform pepMMsMIMIC, (iii) high-throughput docking of the identified compounds with the gp41 MPER peptide, and (iv) molecular dynamics simulations of the docked structures followed by binding free energy calculations. As a result, eight hits-able to mimic pharmacophore properties of bNAb 10E8 by specific and effective interactions with the MPER region of the HIV-1 protein gp41 were selected as the most probable 10E8-mimetic candidates. Similar to 10E8, the predicted compounds target the critically important residues of a highly conserved hinge region of the MPER peptide that provides a conformational flexibility necessary for its functioning in cell-virus membrane fusion process. In light of the data obtained, the identified small molecules may present promising HIV-1 fusion inhibitor scaffolds for the design of novel potent antiviral drugs.

scholarly journals Design, Characterization, and Biopharmaceutical Behavior of Nanoparticles Loaded with an HIV-1 Fusion Inhibitor Peptide

2018 ◽  
Vol 15 (11) ◽  
pp. 5005-5018 ◽  
Author(s):  
Martha Ariza-Sáenz ◽  
Marta Espina ◽  
Ana Calpena ◽  
María J. Gómara ◽  
Ignacio Pérez-Pomeda ◽  
...  
Keyword(s):  
Fusion Inhibitor ◽  
Inhibitor Peptide ◽  
Hiv 1

The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

2020 ◽  
Vol 23 ◽  
Author(s):  
Sisir Nandi ◽  
Mohit Kumar ◽  
Mridula Saxena ◽  
Anil Kumar Saxena
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
The Novel ◽  
In Silico Docking ◽  
Biochemical Mechanisms ◽  
Novel Coronavirus ◽  
In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

Drug repurposing using similarity-based target prediction, docking studies and scaffold hopping of lefamulin

2020 ◽  
Vol 17 ◽  
Author(s):  
Shikha Sharma ◽  
Shweta Sharma ◽  
Vaishali Pathak ◽  
Parwinder Kaur ◽  
Rajesh Kumar Singh
Keyword(s):  
In Silico ◽  
Target Prediction ◽  
Drug Repurposing ◽  
Docking Studies ◽  
Target Protein ◽  
Future Perspective ◽  
Antibacterial Drug ◽  
Scaffold Hopping ◽  
Target Proteins ◽  
Renin Inhibitors

Aim: To investigate and validate the potential target proteins for drug repurposing of newly FDA approved antibacterial drug. Background: Drug repurposing is the process of assigning indications for drugs other than the one(s) that they were initially developed for. Discovery of entirely new indications from already approved drugs is highly lucrative as it minimizes the pipeline of the drug development process by reducing time and cost. In silico driven technologies made it possible to analyze molecules for different target proteins which are not yet explored. Objective: To analyze possible targets proteins for drug repurposing of lefamulin and their validation. Also, in silico prediction of novel scaffolds from lefamulin has been performed for assisting medicinal chemists in future drug design. Methods: A similarity-based prediction tool was employed for predicting target protein and further investigated using docking studies on PDB ID: 2V16. Besides, various in silico tools were employed for prediction of novel scaffolds from lefamulin using scaffold hopping technique followed by evaluation with various in silico parameters viz., ADME, synthetic accessibility and PAINS. Results: Based on the similarity and target prediction studies, renin is found as the most probable target protein for lefamulin. Further, validation studies using docking of lefamulin revealed the significant interactions of lefamulin with the binding pocket of the target protein. Also, three novel scaffolds were predicted using scaffold hopping technique and found to be in the limit to reduce the chances of drug failure in the physiological system during the last stage approval process. Conclusion: To encapsulate the future perspective, lefamulin may assist in the development of the renin inhibitors and, also three possible novel scaffolds with good pharmacokinetic profile can be developed into both as renin inhibitors and for bacterial infections.

scholarly journals In silico design and in vitro expression of novel multiepitope DNA constructs based on HIV-1 proteins and Hsp70 T-cell epitopes

2021 ◽  
Author(s):  
Elahe Akbari ◽  
Kimia Kardani ◽  
Ali Namvar ◽  
Soheila Ajdary ◽  
Esmat Mirabzadeh Ardakani ◽  
...  
Keyword(s):  
T Cell ◽  
In Silico ◽  
T Cell Epitopes ◽  
In Vitro Expression ◽  
In Silico Design ◽  
Hiv 1

3D-QSAR, molecular docking and in silico ADMET studies of propiophenone derivatives with anti-HIV-1 protease activity

2021 ◽  
Author(s):  
Milan Jovanović ◽  
Nemanja Turković ◽  
Branka Ivković ◽  
Zorica Vujić ◽  
Katarina Nikolić ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Protease Activity ◽  
3D Qsar ◽  
In Silico Admet ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Proteomics advances towards developing SARS-CoV-2 therapeutics using in silico drug repurposing approaches

2021 ◽  
Author(s):  
Amrita Mukherjee ◽  
Ayushi Verma ◽  
Surbhi Bihani ◽  
Ananya Burli ◽  
Krishi Mantri ◽  
...  
Keyword(s):  
In Silico ◽  
Drug Repurposing
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