Biology subjects

Capuzzo, A. M.

Publications and source records attributed to Capuzzo, A. M..

3 recordsLinked to original sources

bioRxiv2021

Discovery of potential drug-like compounds against Viral protein (VP40) of Marburg Virus using pharmacophoric based virtual screening from ZINC database.

Marburg virus (MARV) has been confirmed to cause extreme hemorrhagic fever (HFM) in human and animals. The effective and suitable vaccine to treat the MARV virus is not commercialized in public and demands rigorously tested on several scales. This research used a CADD (Computer-Aided Drug Design) computational based technology to find novel drug-like compounds that could inhibit the replicating of the VP40. The pharmacophoric features bases screening was done using an online computational based software, "ZINC Pharmer". We retrieved about 32456 compounds mainly focused on the properties of pharmacophores from the ZINC database. Lipinskis rule was also used to predict these drug-like compounds. as well as molecular coupling-dependent screening and selection of VP40 screening ligand complexes based on S-rank (lower than reference) and value of root, mean square (RMSD) (bottom) to examine for reference) using the Molecular Working Environment (MOE) machine. As a result, 100 compounds were found to have a close interaction with MARV VP40, followed by the Binding energy (BE) analysis of these 100 compounds. Only 50 were the strongest binding energy than favipiravir [reference inhibitor] after using the MOE-LigX algorithm to compare their binding energy. After that, ADMET analysis predicted only five compounds (ZINC95457352, ZINC38752258, ZINC38752253, ZINC39272175, and ZINC38752377) passed the ADMET parameters and have the strongest inhibitory effect against the MARVs VP40. It has been suggested that these "drug-like" candidates have an increased ability to inhibit MARV replication, leading to treatment of MARVD.

bioinformatics↗

bioRxiv2021

Microfluidic Live-Imaging technology to perform research activities in 3D models

One of the most surprising differences observed when comparing cell cultures in 2D and 3D is morphological dissimilarity and their evolution over time. Cells grown in a monolayer tend to flatten in the lower part of the plate adhering to and spreading in the horizontal plane without expanding in the vertical dimension. The result is that cells grown in 2D have a forced apex-basal polarity. 3D cultures support co-cultivation and crosstalking between multiple cell types, which regulate development and formation in the in vivo counterpart. 3D models culture, with or without a scaffold matrix, can exhibit more in vivo-like morphology and physiology. 3D cultures recapitulate relevant physiological cellular processes, transforming into unique platforms for drug screening. To support and guarantee the functional maintenance of a 3D structure, one must consider the structures and dynamics of regulatory networks, increasingly studied with live-imaging microscopy. However, commercially available technologies that can be used for current laboratory needs are limited, although there is a need to facilitate the acquisition of cellular kinetics with a high spatial and temporal resolution, to elevate visual performance and consequently that of experimentation. The CELLviewer is a newly conceived and developed multi-technology instrumentation, combining and synchronizing the work of different scientific disciplines. This work aims to test the system with two models: the first model is a single Jurkat cell while the second is an MCF-7 spheroid. After having grown both models, the two models used are loaded into the microfluidic cartridge for each experiment and recorded in time-lapse for a total of 4 hours. After adaptive autofocus, when sliding inside the cartridge chamber, the samples used are tracked under the action of the optics and the 3D rotation was experimentally successfully obtained. A cell viability assessment was then used using the MitoGreen dye, a fluorescence marker selectively permeable to live cells. The ImageJ software was used to: calculate the model diameter, create fluorescence intensity graphs along a straight line passing through the cell, visualize the spatial fluorescence intensity distribution in 3D.

bioengineering↗

bioRxiv2021

In-silico Structural and Molecular Docking-Based Drug Discovery Against Viral Protein (VP35) of Marburg Virus: A potent Agent of MAVD

The Marburg virus (MARV) is a highly etiological agent of hemorrhagic fever in humans. MARV has spread across the world, including America, Australia, Europe, and different Asia countries. However, there is no approved vaccine to combat MARV, combined with a high mortality rate, which makes antiviral drugs against MARV urgent. The viral protein (VP35) is a core protein of MARV that involves multiple functions of the infection cycle. This research used an in-silico drug design technique to discover the new drug-like small molecules that inhibit VP35 replication. First, several combinations of [~] 4260 showed that structure-based similarity above 90% was retrieved from an online "PubChem" database. Molecular docking was performed using AutoDock 4.2, and ligands were selected based on docking / S score lower than reference CID_5477931 and RMSD value between 1-2. Finally, about 50 compounds showed greater bonding producing hydrogen, Van der Waals, and polar interactions with VP35. After evaluating their binding energy strength and ADMET analysis, only CID_ 3007938 and CID_11427396 were finalized, which showed the most vital binding energy and a strong inhibitory effect with MARVs VP35. The higher binding energy, suitable ADMET, and drug similarity parameters suggest that these "CID_ 3007938 and CID_11427396" candidates have incredible latency to inhibit MARV replication; hence, these strengths led to the treatment of MAVD.

bioinformatics↗