Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study

Abstract

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.

Recent progress in understanding 2019 novel coronavirus (SARS-CoV-2) associated with human respiratory disease: detection, mechanisms and treatment

“…JID: ANTAGE [m5G; April 11, 2020;23:32 ] virus RdRp to inhibit RNA synthesis [67] . It has been shown in in vitro experiments that ribavirin inhibits the replication of MERS-CoV and HCoV-OC43, but the dosage that produces a significant effect is not within the range of typical human therapies [68] .…”

Potential Impact of SARS-CoV-2 Infection in HIV-positive Patients in South Africa

“…(36) A further study was undertaken, in which the RNA-dependent polymerase (RdRp) of SARS-CoV-2 was modelled, validated and then targeted using anti-polymerase drugs currently registered for use against various viruses (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir and Tenofovir). (37) RdRp is a crucial viral enzyme in the life cycle of RNA viruses. In that study, these antiviral agents were shown to be able to bind tightly to RdRp of the SARS-CoV-2 virus and thus could possibly be useful for the treatment of this infection.…”

Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies

“…Among the main actors of SARS-CoV-2 infection the SARS-CoV-2 spike proteins, RNA dependent RNA polymerases and proteases deserve to be mentioned. Indeed, RNA dependent RNA polymerase has become one of the main targets of a nucleoside analog antiviral drug, the remdesivir, already used for reducing complications due to Ebola, Dengue and MERS-CoV infections (1)(2)(3)(4)(5)(6). At the same time viral protease inhibitors (7)(8)(9)(10) are under investigation for their ability in preventing virus protein (with specific reference to spike proteins) cleavage (11) leading to the fusion of virus proteins with host cell membranes.…”