Repurposing drugs for inhibitory activity against nonstructural proteins catalytic complex from COVID-۱۹ by molecular modeling

Background and Aim : Nonstructural proteins (NSPS) is a piece of multisubunit machinery that catalyzes the synthesis of viral RNA and plays a central role in the replication and transcription cycle of the COVID-۱۹ virus. NSP۱۲ is considered a primary target for nucleoside analog antiviral inhibitors, which shows the potential treatment of COVID-۱۹ viral infections. To discover new inhibitor this target we run virtual screening workflow for discovery new potential drugs.Methods : For all molecular modeling, the Small-Molecular Drug Discovery Suite ۲۰۱۵-۲ (Schrodinger, LLC, New York, NY, ۲۰۱۶) was used. The molecular modeling was subjected using the Glide application in the Schrödinger drug discovery suite. More than ۵۰۰۰ drugs downloaded from ZINC۱۵ were prepared with Ligprep application; proteins were obtained from a protein data bank (PDB). The Protein Preparation and Prime application were performed to minimize the protein strains state.Results : The results of molecular modeling showed that compounds with ZINC ID ۸۵۵۵۲۱۱۴ (Maltotetraose), ۲۵۲۲۸۶۸ (Nystatin) and ۶۰۱۸۳۱۷۰ (Paromomycin) demonstrated docking score -۱۴.۲۵۰, -۱۲.۲۱۴ and -۱۲.۰۱۳ Kcal.mol-۱ had the highest inhibitory activity on NSPS catalytic complex and RNA dependent RNA polymerase replication activity, respectively.Conclusion : Regarding the importance of finding a safe, cheap, easy to industrialize as fast as a possible cure for the worldwide pandemic, COVID-۱۹, the inhibitory activity of maltotetrose, nystatin and Paromomycin against NSPS catalytic complex has been investigated by molecular docking and could be carried on in future researches. all authors were equally contributed.

کلیدواژه ها:

Repurposing ، Molecular modeling ، COVID-۱۹ ، NSPS complex