Molecular Docking and Analysis of In Silico Generated Ligands against SARS-CoV-2 Spike and Replicase Proteins

Abstract

Purpose: The novel coronavirus also known as coronavirus disease 2019 (COVID-19), or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which broke out in the latter part of the year 2019, took the entire human race unawares. This sis due to its devastating health, social and economic consequences. In this study, the ability of some small molecules to interact with some SARS-CoV-2 proteins was investigated in silico for the purpose discovering molecules which can be employed in the areas COVID-19 diagnosis and treatment. Methodology: By way of molecular docking, a library of in silico generated ligands was docked to SARS-CoV-2 spike and replicase proteins to identify leads with propensity to bind them with high affinity. The identified leads proved to bind these proteins with stronger affinity than the native ligand aiding in their in vivo metabolic processes. Findings: It was observed that spike protein binds to its cellular receptor with binding affinity of -4.8Kcal/mol; it binds to a non cellular analogue with -5.4, while 4twy 3BL and 5n19 D03 bind spike protein with binding affinities of -7.3Kcal/mol each. They also bind replicase protein with -8.2 and -7.2 Kcal/mol respectively. 5c8s G3A and 2d2d ENB were identified as the most suitable leads for SARS-CoV-2 spike protein detection, while 3d62 959 and 1r4l XX5 were identified as leads with most suitable druglikeness against SARS-CoV-2. These findings indicate that the identified ligands can preferentially displace or inhibit binding of the viral proteins to their native endogenous ligands and that both cellular attachment through spike and ACE2 interaction, and viral replication process can both be inhibited by using just one of the substances identified. This study is part of efforts in finding non recombinant nucleic acid solutions to SARS-CoV-2 diagnosis and treatment. If these findings are implemented, they can enhance efficient detection of the virus antigens from biological samples. Conclusion: Identifying molecules that can interact with SARS-CoV-2 proteins could optimize diagnostic and therapeutic care for patients infected with the virus. Recommendation: Based on the study, 5c8s G3A and 2d2d ENB were identified as the most suitable leads that are favorably disposed for SARS-CoV-2 spike protein detection from biological samples. Also, 3d62 959 and 1r4l XX5 were identified as leads with most suitable drug likeness against SARS-CoV-2 based on the filters from SwissADME and Molinspiration cheminformatics and therefore deserve further in vitro and in vivo evaluations.