Elucidating the role of N440K mutation in SARS-CoV-2 spike – ACE-2 binding affinity and COVID-19 severity by virtual screening, molecular docking and dynamics approach

Abstract

COVID-19 has become a public health concern around the world. The frequency of N440K variant was higher during the second wave in South India. The mutation was observed in the Receptor Binding Domain region (RBD) of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spike (S) protein. The binding affinity of SARS-CoV-2-Angiotensin-Converting Enzyme-2 (ACE-2) plays a major role in the transmission and severity of the disease. To understand the binding affinity of the wild and mutant SARS-CoV-2 S with ACE2, molecular modeling studies were carried out. We discovered that the wild SARS-CoV-2 S RBD-ACE-2 complex has a high binding affinity and stability than that of the mutant. The N440K strain escapes from antibody neutralization, which might increase reinfection and decrease vaccine efficiency. To find a potential inhibitor against mutant N440K SARS-CoV-2, a virtual screening process was carried out and found ZINC169293961, ZINC409421825 and ZINC22060839 as the best binding energy compounds.

Communicated by Ramaswamy H. Sarma.

Keywords:

• COVID-19
• SARS-CoV-2
• binding energy
• elbasvir analogues
• public health
• maraviroc analogues
• simeprevir analogues

Authors’ contributions

MK, SKM performed the research and wrote the paper. M.K, UM, JMA,VVR, SKM – designed the research study. SKM – supervised the work.

Acknowledgement

MK, JMA and SKM would like to thank the management of PMCHRI for providing the necessary facilities to carry out this research work.

Disclosure statement

The authors declare that there is no conflict of interest.