Virtual Screening of FDA Approved Drugs Library to Identify a Potential Inhibitor against NS2B-NS3 Protease of Yellow Fever Virus

Abstract

Yellow fever is a neglected hemorrhagic disease with a high case fatality rate ranging between 25% and 50% for the hospitalized patients. Yellow fever disease is caused by a zoonotic pathogen known as yellow fever virus. This RNA virus is usually transmitted by mosquitos and it is considered endemic in the tropical regions of South America and Africa. Although an effective vaccine is available for yellow fever virus, no antiviral drug is yet licensed against the disease. Thus, yellow fever virus is still representing a re-emerging threat among unvaccinated individuals in endemic regions. The NS2B-NS3 protease seems to play an important role in yellow fever virus replication cycle. As such, the NS2B-NS3 protease may represent a potential target for structure-based drug design and discovery. In this direction, computational approaches like virtual screening can be utilized to hasten the design of novel antivirals and/ or repurposing an already FDA approved drugs. In this in silico study, an FDA approved drugs library was screened against NS2B-NS3 protease crystal of yellow fever virus. Then the best hits with least energy of binding and ability of hydrogen bonding with key residues of protease active site were then selected and submitted to molecular dynamics simulation. And throughout simulation interval, only Olsalazine was able to stay in close proximity to the active site of protease crystal with least average MM-PBSA binding energy as compared to Dantrolene, Belinostat and Linezolid. This indicates that Olsalazine may have the best capacity to bind to NS2B-NS3 protease and interfere with its activity.

Computational Repurposing of FDA Approved Drugs Against Monkeypox Virus Cysteine Proteinase: A Molecular Docking and Dynamics Simulation Study.

“…The methodology applied in this study is similar to what we have employed in our previously published articles [14][15][16][17]. In summary, a library of 1,615 FDA approved drugs was obtained from ZINC database (https://zinc.docking.org/).…”

Molecular docking and dynamics simulation analysis of the human FXIIa with compounds from the Mcule database

“…It is well-known that ligand proximity to the target active site during simulation usually refers to stronger ligand binding to its target. This ligand proximity to target active site can be estimated by calculating ligand movement Root Mean Square Deviation (RMSD) throughout simulation [ 32 , 33 ]. As such, we have evaluated the mean RMSD value for ligand movement from target active site during simulation and subsequently eliminated those hits with mean RMSD value greater than 4 Angstrom.…”

Dantrolene and ryanodine receptors in COVID‐19: The daunting task and neglected warden

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