title: Zika virus NS5 protein potential inhibitors: an enhanced in silico approach in drug discovery.
abstract: The re-emerging Zika virus (ZIKV) is an arthropod-borne virus that has been described to have explosive potential as a worldwide pandemic. The initial transmission of the virus was through a mosquito vector, however, evolving modes of transmission has allowed the spread of the disease over continents. The virus has already been linked to irreversible chronic central nervous system conditions. The concerns of the scientific and clinical community are the consequences of Zika viral mutations, thus suggesting the urgent need for viral inhibitors. There have been large strides in vaccine development against the virus but there are still no FDA approved drugs available. Rapid rational drug design and discovery research is fundamental in the production of potent inhibitors against the virus that will not just mask the virus, but destroy it completely. In silico drug design allows for this prompt screening of potential leads, thus decreasing the consumption of precious time and resources. This study demonstrates an optimized and proven screening technique in the discovery of two potential small molecule inhibitors of ZIKV Methyltransferase and RNA dependent RNA polymerase. This in silico 'per-residue energy decomposition pharmacophore' virtual screening approach will be critical in aiding scientists in the discovery of not only effective inhibitors of Zika viral targets, but also a wide range of anti-viral agents.
authors.affiliation: a Molecular Modeling and Drug Design Research Group , School of Health Sciences, University of KwaZulu-Natal , Westville Campus, Durban 4001 , South Africa.
authors.forename: Pritika
authors.initials: P
authors.lastname: Ramharack
authors.affiliation: a Molecular Modeling and Drug Design Research Group , School of Health Sciences, University of KwaZulu-Natal , Westville Campus, Durban 4001 , South Africa.|b Pharmaceutical Sciences , University of KwaZulu-Natal , Westville Campus, Durban 4001 , South Africa.|c Faculty of Pharmacy, Department of Pharmaceutical Organic Chemistry , Zagazig University , Zagazig , Egypt.|d College of Pharmacy and Pharmaceutical Sciences, Florida Agricultural and Mechanical University, FAMU , Tallahassee , FL 32307 , USA.
authors.forename: Mahmoud E S
authors.initials: MES
authors.lastname: Soliman
mesh_terms: D000465:Algorithms; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects; D000071244:Zika Virus / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D017361:Viral Nonstructural Proteins
keywords: NS5 protein potential inhibitors; Zika virus per-residue decomposition based pharmacophore; binding free energy; molecular dynamic simulations; virtual screening