Potential Trends for COVID-19 Fighting: An Immuno-informatics Overview

Public health care capacity is currently overwhelmed by pandemic outbreak of coronavirus disease 2019. This respiratory disease is a real threat especially for those elderly people with comorbidities. The disease can progress into acute respiratory distress syndrome which can be fatal. No vaccine or drug had been developed against any human coronaviruses due to cessation of previous epidemics and withdrawal of assigned funds. Currently, humanity is in a real challenge to accelerate the development of effective drug and vaccine against severe acute respiratory syndrome coronavirus 2. Till now, computational approaches have played a substantial role for analysis of viral structure and also development of both drug and vaccine candidates in an accelerated pace. Some of these therapeutic designs have found their way into clinical trials. Here, we will overview different immuno-informatics attempts, targets and ideas as possible trends to counteract coronavirus disease 2019

LIGAND-BASED VIRTUAL SCREENING OF FDA APPROVED DRUGS TO IDENTIFY NEW INHIBITORS AGAINST LACTATE DEHYDROGENASE ENZYME OF MALARIA PARASITES

Objective: The aim of this study is to computationally repurpose FDA approved drugs as potential inhibitors of the Plasmodium falciparum lactate dehydrogenase (PfLDH) by competing with the cofactor NADH. Methods: In this in-silico study, we have virtually screened a library of FDA approved drugs for structural similarity to the dihydronicotinamide adenine dinucleotide (NADH). Then, the top hits were further assessed for clinical safety and by application of molecular docking and dynamics simulation. Results: Ligand-based virtual screening reports that the antibiotic Novobiocin has a good similarity to the cofactor NADH with a score of 0.7. Also, molecular docking study indicates that Novobiocin may has the ability to interact with PfLDH enzyme with a docking energy of -8.8 Kcal/ mol. However, during molecular dynamics (MD) simulation, the mean ligand proximity root mean square deviation (RMSD) and binding energy for Novobiocin were 4.3 Angstrom and -37.45 Kcal/ mol respectively. These MD simulation parameters are inferior to those recorded for NADH molecule during 50 nanoseconds interval. Conclusion: The antibiotic Novobiocin may serve as a potential lead candidate toward the design of novel antimalarial agents. However, further evaluation of Novobiocin may be recommended to affirm its capacity against PfLDH enzyme

VIRTUAL SCREENING OF FDA APPROVED DRUGS BY MOLECULAR DOCKING AND DYNAMICS SIMULATION TO RECOGNIZE POTENTIAL INHIBITORS AGAINST MYCOBACTERIUM TUBERCULOSIS ENOYL-ACYL CARRIER PROTEIN REDUCTASE ENZYME

Objective: This in-silico study is aimed at identification of new possible inhibitors against Mycobacterium tuberculosis InhA enzyme by screening a library of FDA approved drugs. Methods: In this in-silico study, a library of FDA approved drugs was screened by molecular docking against the monomer of enoyl-acyl carrier protein reductase to recognize potential inhibitors. Then, those best drugs with minimum docking energy were subjected to molecular dynamics simulation. Results: Out of the top ten docking hits, only revefenacin was able to maintain the closet proximity to InhA enzyme binding pocket during the two rounds of dynamics simulation. Analysis of molecular dynamics (MD) simulation data indicated that the antimuscarinic drug revefenacin has a ligand movement Root-Mean-Square Deviation (RMSD) that didn’t exceed 4 Angstrom. Also, in this MD study, revefenacin has a superior binding energy of -35.59 Kcal/ mol as compared to -13.88 Kcal/mol for the other hit ergotamine. These favorable MD simulation records for revefenacin can be explained by its ability to continuously interact with enzyme binding pocket by two hydrogen bonds. Conclusion: We report that the antimuscarinic drug revefenacin may have the potential to inhibit the enoyl-acyl carrier protein reductase for Mycobacterium tuberculosis. However, these preliminary results must be further evaluated by in vitro and in vivo studies