Journal Pre-proof J o u r n a l P r e -p r o o f Abstract Aims: A new human coronavirus (HCoV), which has been designated SARS-CoV-2, began spreading in December 2019 in Wuhan City, China causing pneumonia called COVID-19.The spread of SARS-CoV-2 has been faster than any other coronaviruses that have succeeded in crossing the animal-human barrier. There is concern that this new virus will spread around the world as did the previous two HCoVs-Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)-each of which caused approximately 800 deaths in the years 2002 and 2012, respectively. Thus far, 11,268 deaths have been reported from the 258,842 confirmed infections in 168 countries. Main methods: In this study, the RNA-dependent RNA polymerase (RdRp) of the newly emerged coronavirus is modeled, validated, and then targeted using different anti-polymerase drugs currently on the market that have been approved for use against various viruses. Key findings: The results suggest the effectiveness of Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir as potent drugs against SARS-CoV-2 since they tightly bind to its RdRp. In addition, the results suggest guanosine derivative (IDX-184), Setrobuvir, and YAK as top seeds for antiviral treatments with high potential to fight the SARS-CoV-2 strain specifically. Significance: The availability of FDA-approved anti-RdRp drugs can help treat patients and reduce the danger of the mysterious new viral infection COVID-19. The drugs mentioned above can tightly bind to the RdRp of the SARS-CoV-2 strain and thus may be used to treat the disease. No toxicity measurements are required for these drugs since they were previously tested prior to their approval by the FDA. Keywords Journal Pre-proof J o u r n a l P r e -p r o o f COVID-19; SARS-CoV-2; RdRp; molecular docking; structural bioinformatics; drug repurposing 19 outbreak (Yang, 2020). Ten days later, the WHO declared COVID-19 to be a Public Health Emergency of International Concern (PHEIC), then COVID-19 is declared as a pandemic 40 days later by the WHO. The symptoms of COVID-19 include fever, malaise, dry cough, shortness of breath, and respiratory distress (Hui et al., 2020). Journal Pre-proof drugs, either currently on the market or in clinical trials, to stop the infection immediately. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir showed promising results for use against the newly emerged strain of coronavirus. Besides, the IDX-184, Setrobuvir, and YAK compounds exhibited excellent results for binding SARS-CoV-2 RdRp. We suggest utilizing GTP as a seed to obtain specific inhibitors against SARS-CoV-2 RdRp using its high-quality model. Journal Pre-proof J o u r n a l P r e -p r o o f Acknowledgment: Mrs. Kauther M Shaltoot is appreciated for her kind help and support; without her, this work was not possible. Prof. Dr. Wael Elshemey is appreciated for guidance and performing the docking calculations on his computational facility.

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Objectives: Understanding the novel coronavirus (COVID-19) mode of host cell recognition may help to fight the disease and save lives. The spike protein of coronaviruses is the main driving force for host cell recognition. Methods: In this study, the COVID-19 spike binding site to the cell-surface receptor (Glucose Regulated Protein 78 (GRP78)) is predicted using combined molecular modeling docking and structural bioinformatics. The COVID-19 spike protein is modeled using its counterpart, the SARS spike. Results: Sequence and structural alignments show that four regions, in addition to its cyclic nature have sequence and physicochemical similarities to the cyclic Pep42. Protein-protein docking was performed to test the four regions of the spike that fit tightly in the GRP78 Substrate Binding Domain β (SBDβ). The docking pose revealed the involvement of the SBDβ of GRP78 and the receptor-binding domain of the coronavirus spike protein in recognition of the host cell receptor. Conclusions:We reveal that the binding is more favorable between regions III (C391-C525) and IV (C480-C488) of the spike protein model and GRP78. Region IV is the main driving force for GRP78 binding with the predicted binding affinity of -9.8 kcal/mol. These nine residues can be used to develop therapeutics specific against COVID-19.