Structure, Properties, and Drug-likeness of Pharmaceuticals That Inhibit Ebola Virus Disease (EVD) Proliferation

Introduction: The Ebola virus is one of known viruses within the genus Ebolavirus that are generally
considered to cause Ebola virus disease (EBV) in humans. Some investigators have determined that
Ebola virus outbreaks have an increased likelihood to occur when temperatures are lower and
humidity is higher. The determination and evaluation of pharmacokinetic and pharmacodynamics
properties of drugs potentially useful for treatment of Ebola virus disease is a very important
consideration for discovery of new pharmaceuticals.
Aims: To present the molecular structures of compounds that has been shown to inhibit the
proliferation of Ebola virus. To elucidate the molecular properties of these virus inhibiting compounds.
Study Design: The molecular properties of virus inhibiting compounds are elucidated and compiled.
Pattern recognition methods and statistical analysis are applied to determine optimal properties of this
group of compounds.
Place and Duration of Study: Chemistry Department, Durham Science Center, University of
Nebraska, Omaha NE. between December 2015 and February 2016.
Methodology: A total of 60 compounds were identified as inhibiting the virus Ebola. The molecular
properties such as Log P, molecular weight, and 7 other descriptors were elucidated utilizing heuristic
methods. Structures are compared by applying classification methods with statistical tests to
determine trends, underlying relationships, and pattern recognition.
Results: For 60 compounds identified the averages determined: for Log P (3.51), polar surface area
(89.45 Angstroms2), molecular weight (432.6), molecular volume (393.96 Angstroms3), and number of
rotatable bonds (7). Molecular weight showed a strong positive correlation to number of oxygen and
nitrogen atoms, number of rotatable bonds, and molecular volume. K-means clustering indicated
seven clusters divided according to highest similarity of members in the cluster. Ranges found:
formula weights (157.1 to 822.94), Log P (-2.24 to 8.93), polar surface area (6.48 to 267.04 A2), and
number of atoms (11 to 58). Multiple regression analysis produced an algorithm to predict similar
compounds.
Conclusion: The formula weights and Log P values of Ebola virus inhibitors show a broad range in
numerical values. Consistency in properties was identified by statistical analysis with grouping for
similarity by K-means pattern recognition. Multiple regression analysis enables prediction of similar
compounds as drug candidates. Only 29 compounds showed zero violations of rule of 5, an indication
of favorable drug-likeness. These compounds are highly varied in structures and properties.