Novel guanosine derivatives against MERS CoV polymerase: An in silico perspective

Abstract

The Middle East Respiratory Syndrome Coronavirus (MERS CoV), also termed camel flu, is a new viral infection that first reported in the year 2012 in the Middle East region and further spread during the last seven years. MERS CoV is characterized by its high mortality rate among different human coronaviruses. MERS CoV polymerase shares more than 20% sequence identity with the Hepatitis C Virus (HCV) Non-structural 5b (NS5b) RNA dependent RNA polymerase (RdRp). Despite the low sequence identity, the active site is conserved between the two proteins, with two consecutive aspartates that are crucial in the nucleotide transfer reaction. In this study, seven nucleotide inhibitors have been tested against MERS CoV RdRp using molecular modeling and docking simulations, from which four are novel compounds. Molecular Dynamics Simulation for 260 nanoseconds is performed on the MERS CoV RdRp model to test the effect of protein dynamics on the binding affinities to the tested nucleotide inhibitors. Results support the hypothesis of using the anti-polymerases (Anti-HCV drugs) against MERS CoV RdRp as a potent candidates. Besides four novel compounds are suggested as a seed for high performance inhibitors against MERS CoV RdRp.

Communicated by Ramaswamy H. Sarma

Keywords:

• MERS CoV
• polymerase
• molecular dynamics simulation
• molecular docking
• HCV NS5b RdRp

Acknowledgments

The authors are thankful to Dr. Khaled Barakat for his revision of the manuscript. MDS is conducted on the Cy-Tera supercomputing facility of the Cyprus Institute of science (Project number pro15b114s1).

Disclosure statement

No potential conflict of interest was reported by the authors.