**6. Remdesivir (GS-5734)**

In 2009, Gilead Sciences, Inc. (USA) developed an antiviral drug called Remdesivir (RDV) to treat hepatitis B [48]. It did not indicate a desirable act against hepatitis. However, it is effective against other viruses, such as the Nipah virus, hepatitis C, and Marburg [49]. RDV is a broad-spectrum antiviral nucleoside analog, and

#### **Figure 2.**

*Common inhibitory action of antiviral drugs.*

#### *Antiviral Drugs and Their Roles in the Treatment of Coronavirus Infection DOI: http://dx.doi.org/10.5772/intechopen.101717*

now it is used as a treatment option for COVID-19 [50]. It is the class of polymerase inhibitors and showed activity against different RNA viruses, including SARS-CoV, MERS-CoV, Lassa fever virus, Junin virus, respiratory syncytial virus, Nipah virus, Hendra viruses, filoviruses, and Ebola viruses. RDV is a prodrug of its parent adenosine triphosphate analog, (2R,3R,4S,5R)-2-(4-aminopyrrolo(2,1-f)(1,2,4) triazin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)oxolane-2-carbonitrile (GS-441524), and has similarity to the adenine nucleic acid structurally. Both of these drugs are metabolized into the active component as nucleoside triphosphate (GS-443902) after ingestion and show antiviral activity against SARS-CoV [51]. RDV targets the viral genome replication process by acting as an RdRp inhibitor [52], RDV was used to block the RNA-dependent RNA polymerase of SARS-CoV-2. On metabolization of RDV into active nucleoside triphosphate (NTP), which competes with ATP for incorporation into nascent RNA strands, premature RNA synthesis occurs, resulting in RNA strand termination and cessation of growth [51]. RDV when tested through in vitro studies using the Vero E6 cells showed an EC50 value of 1.76 μM that showed its activity against SARS-CoV-2 [53]. Intravenous remdesivir treatment showed significant improvement for COVID-19. RDV and chloroquine are highly effective in the control of SARS-CoV-2 infection. In severe COVID-19 treated with RDV, improvements in the clinical finding were observed in 68% of patients [54]. However, in October 2020, the WHO removed it from the list of effective drugs in the treatment procedure of COVID-19 patients because it failed in the first trials for the treatment of COVID-19 [42]. There are still controversies regarding the results, no benefit in COVID-19 treatment using RDV; whereas, the company claims it as a promising drug for the same. After penetrating the cell, RDV as a prodrug (GS-5734) and like Favipiravir, binds to the triphosphate group under esterase, kinase, and phosphatase enzymatic reactions. These enzymes modify the structure of RDV and convert it to the active form, RDV-triphosphate (RDV-TP or GS-441524) [55]. After virus entry into the cell cytoplasm, this prodrug gets activated and loses its ability to diffuse to the intercellular space [53]. However, the primary mechanism of action of RDV against SARS-CoV-2 is unclear, and more research is necessary to understand it [56]. In an in vitro study, the combination of RDV and chloroquine (antimalarial drug) effectively inhibited SARS-CoV-2 growth in Vero E6 cells [19]. RDV is used to treat COVID-19 cases.

The combined use of RDV and IFN-β created a higher antiviral activity compared with the lopinavir/ritonavir-IFN-β combination against the MERS-CoV virus. Additionally, RDV could be better pulmonary function, cause fall lung viral loads and severe lung pathology in mice; on the contrary, lopinavir/ritonavir-IFN-β could not [57]. In two clinical studies, the use of RDV has been carried out against severe or mild respiratory infections caused by COVID-19. Recently, RDV for emergency use to treat COVID-19, including five antiviral drugs, ribavirin, RDV, sofosbuvir, galidesivir, and tenofovir, was conducted against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp); these drugs showed promising results against COVID-19. Prominent adverse reactions were an acute respiratory failure, decreased glomerular filtration rate, lymphocytopenia, pyrexia, hyperglycemia, increased anemia, increased creatine, and liver transaminases. RDV given in combination with baricitinib (Janus kinase inhibitor used to hinder intracellular signaling of cytokines) was effective compared with RDV alone in terms of reducing recovery time additionally speeding improvement. RDV's parent nucleotide GS-441524 is superior and less toxic than its prodrug form and has shown efficacy [58].
