Many countries in the world have recently experienced an outbreak of COVID-19, turned out to be a pandemic which significantly affected the world economy. Among many attempts to treat/control infection or to modulate host immunity, many small molecules including steroids were prescribed based on their use against other viral infection or inflammatory conditions. A recent report established the possibility of usage of a corticosteroid against the virus through inhibiting NSP-15; an mRNA endonuclease of SARS-CoV-2 and thereby viral replication. This study aimed to identify potential anti-viral agents for the virus through computational approaches and to validate binding properties with the protein target through molecular dynamics simulation. Unlike the conventional approaches, dedicated data base of steroid like compounds was used for initial screening along with dexamethasone and cortisone, which are used in the treatment of COVID-19 affected population in some countries. Molecular docking was performed for three compounds filtered from data base in addition to dexamethasone and Cortisone followed by molecular dynamics simulation analysis to validate the dynamics of binding at the active site. In addition, analysis of ADME properties established that these compounds have favorable drug-like properties. Based on docking, molecular dynamics simulation studies and various other trajectory analyses, compounds that are identified could be suggested as therapeutics or precursors towards designing new anti-viral agents against SARS-CoV-2, to combat COVID-19. Also, this is an attempt to study the impact of steroid compounds on NSP-15 of SARS-CoV-2, since many steroid like compounds are used during the treatment of COVID-19 patients.
Keywords: COVID-19; Dexamethasone; Endoribonuclease; Molecular docking; NSP-15; Principal component analysis; SARS-CoV-2; Steroids.
© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.