Abstract: Muthusamy et al., J Virol Antivir Res 2021, 10:4 Journal of Virology & Antiviral Research Research Article Virtual Screening Reveals Potential Anti-Parasitic Drugs Inhibiting the Receptor Binding Domain of SARS-CoV-2 Spike protein Sathya Muthusamy, Hariprabu Gopal, Thiliban Manivarma, Satya Narayan Pradhan, Prince. R. Prabhu* Abstract The 2019’s COVID-19 outbreak which spread to over 200 countries across the globe had its origin from the 2002’s SARS-CoV-1 epidemic. The corona viruses are single stranded positive sense RNA viruses with 4 structural proteins such as spike(S), membrane(M), envelope(E) and nucleocapsid(N) proteins and 16 non-structural proteins (NSPs). The spike(S) protein is a homo-trimer protruding from the viral surface comprising 2 subunits namely, the S1 and S2 where the S1 subunit consists of the receptor binding domain (RBD) and the S2 subunit consists of the fusion peptide. The spike glycoprotein is considered as the most desired pharmacological target for drug designing, thus blocking the viral entry into the host. Computer-Aided Drug Designing significantly reduces the cost and time in drug discovery compared to the in-vitro methods. Hence in our study, we have performed a virtual screening of the complete set of anti-parasitic drugs using the popular molecular docking tool, Autodock vina with an aim to repurpose the potential hits for the SARS-CoV-2 infection. The repurposed drugs are advantageous for their easy and immediate access owing to their already proven safety records in toxicity and hence are better than novel drugs. Our results revealed 32 anti-parasitic compounds crossing our threshold binding affinity with selamectin, ivermectin, artefenomel, moxidectin, posaconazole, imidocarb, piperaquine, cepharantine, betulinic acid and atovaquone at the top of the list and occupying the three different electrostatic regions in the RBD. Further optimization strategies and in-vitro trials could make our potential anti-parasitic hits, a potential cure for the SARS-CoV-2 infection. Keywords Virtual screening; SARS-CoV-2; COVID-19; Spike protein; Receptor Binding Domain; Autodock Vina, Antiparasitic drugs; Anti-viral; Repurposed drugs. Abbreviations COVID-19: COrona VIrus Disease 2019; SARS-CoV-1: Severe Acute Respiratory Syndrome-Corona Virus-1; SARS-CoV-2: Severe Acute Respiratory Syndrome-Corona Virus-2; S protein: Spike protein; RBD:Receptor Binding Domain; ACE-2: Angiotensin Converting Enzyme-2; NSP: Non Structural Protein; RNA: Ribo Nucleic Acid; CDC: Centre for Disease Control and Prevention; WHO: World Health Organization; RT-PCR: Reverse Transcription *Corresponding author: Prince. R. Prabhu, Department of Biotechnology, Anna University, Chennai--600025, Email: princeprp@gmail.com, Phone: +91 9840924463 Received: June 13, 2021 Accepted: July 08, 2021 Published: July 08, 2021 International Publisher of Science, Technology and Medicine A SciTechnol Journal Polymerase Chain Reaction; GISAID: Global Initiative on Sharing All Influenza Data; HR-1: Heptad Repeat 1; HR-2: Heptad Repeat 2; CADD: Computer-Aided Drug Design; FDA: Food and Drug Administration; GABA: Gamma-Amino Butyric Acid; CNS: Central Nervous System; BBB: Blood Brain Barrier; CASF: Comparative Assessment of Scoring Function; PDB: Protein Data Bank; SDF: Structure Data File; cryo-EM: cryogenic Electron Microscopy; RCSB: Research Collaboratory for Structural Bioinformatics; C-I-TASSER: Contact-guided Iterative Threading ASSembly..