In silico discovery of drugs targeting PLpro and Nsp12 RNA polymerase of SARS-CoV-2.

Research Report.

EXECUTIVE SUMMARY: Severe acute respiratory syndrome- coronavirus 2(SARS_CoV-2) has infected over 200 million and killed over 4.33 million people worldwide since August 1, 2021, and effective treatment options are yet to be discovered. In recent years, several in vivo and in vitro screening of hits approaches have given a preference of study insufficiently explored natural products from different sources such as compounds collection from various institutions, combinatorial chemistry libraries, and databases in a hope to identify an new unique antiviral agent. PLpro is required for processing viral poly proteins to generate a functional replicate complex and implicated in cleaving proteinaceous post-translational modifications on host proteins, and NSP 12, also known as RNA-dependent RNA polymerase catalyzes the synthesis of viral RNA thus considered as a central component in the life cycle of viral, making them potential targets for anti-SARS drug discovery. This project aims to discover drugs targeting protease and helicase of SARS-CoV-2via virtual screening- a computer-based approach of manually curated lichen metabolites ligand library. Further, we will analyze the potential ligands absorption, distribution, metabolism and excretion - toxicity (ADMET). Over 250lichen metabolites were screened from the manually curated lichen library. we prepared a list of the top 5 ligands for each protein targets based on the CDOCKER interacting energy. Considering predicted ADMET and drug-likeness profiles four promising leads were identified. IN conclusion, we identified a potential lead for antiviral drug discovery against the SARS-COV-2.Our results will aid global efforts to find safe and effective remedies for COVID-19. Keywords: SARS-CoV-2, metabolites, molecular docking, Drug discovery studio.