COVID-19 consists of long polymers bounded by nucleocapsids, and it spreads through a variety of routes, including aerosolized transmission, fecal-oral transmission, droplets, and surface transmission. The disease affects multiple organs including the lungs, heart, and kidneys. There is a possibility of respiratory failure, pneumonia, or even death due to infections. It is common to suffer from acute lung and renal injuries and shock. The virus is detected by PCR testing from nasopharyngeal swabs. The virus and illness that Covid-19 causes are unknown, and there are no treatments available. There is no specific treatment available without symptomatic treatment [1].

The drug favipiravir is used to stop SARS-CoV-2 signs. A spike in research occurred after COVID-19 broke out to find a cure or medication. In order to combat COVID-19 (Coronavirus disease), triggered by the SARS-CoV-2 virus, a variety of drugs may be used, including favipiravir and others [2]. The drug favipiravir obstructs RNA-dependent RNA polymerase (RdRp) in RNA viruses in a broad-based and potent manner. Since January 12, 2021, more than 88 million cases along with 1.9 million mortality cases have been reported worldwide [3]. Despite the difficulty of predicting the threshold [4], SARS-CoV-2 spread is unlikely to stop until at least 50% of the population is immune, either through vaccination or after recovering from a naturally acquired infection [5]. There are now some promising vaccine candidates approved by the FDA [6] in an emergency situation. It is, however, anticipated that global access to the necessary level will be delayed until the pandemic reaches the population impact level.

As shown in Table 1, Coronavirus causes disease in humans and their cellular receptors.

The covid-19 pandemic has led to few effective treatments being developed to cope with this disease. Initially, favipiravir was applied to SARS-CoV-2 in Wuhan, where the epicenter of the pandemic was located. Italian authorities approved the prescription of the drug for emergency purposes after the pandemic spread to Europe. The drug is currently being marketed in Japan, Russia, Ukraine, Uzbekistan, Moldova, and Kazakhstan. Regions like Saudi Arabia and the United Arab Emirates have also delivered the respective approval to the said drug. Afterward, Turkey, Bangladesh, and most recently Egypt launched this agent for commercial use category. In the year 2020 during the month of June approval of favipiravir was received for mild and moderate cases of COVID-19 infections in India from the DCGI. On Clinical Trials Gov, there were 32 studies registered as of the 23rd of July, 2020; three are complete, and 12 (twelve) are recruiting [7].

According to the Japanese Pharmaceuticals and Medical Devices Agency, favipiravir (AVIGAN^®) was approved for the treatment of acute and re-emerging influenza virus infections in 2014 [8]. The majority of studies have reported its effectiveness against other RNA viruses, such as Ebola viruses [8, 9] or rhinoviruses and respiratory syncytial viruses [10]. The 50% effective concentration (EC50) of favipiravir against SARS-CoV-2 was reported to be 61.88 μM/L in Vero E6 cells in vitro studies. Therefore, favipiravir is highly effective at treating COVID-19 patients. Despite this, there is very limited research examining the safety as well as efficacy aspects of favipiravir in COVID-19 patients.

The viral inhibitory activity of favipiravir (T-705) was first identified during the study of chemical agents that can neutralize influenza viruses in the chemical library of Toyoma chemicals [11]. There were antiviral activities linked with the first compound, A/PR/8/34, which was later, named asT-1105, and it’s their associated derivatives. The pyrazine moiety in the structure of T-1105(2) was chemically modified to yield the drug favipiravir.

According to studies conducted on healthy Japanese volunteers, the maximum plasma concentration of favipiravir occurred 2 hours after oral administration, and then the concentration decreased rapidly with a half-life of 2 to 5.5 hours [12]. Favipiravir is administered as a prodrug. In addition to its excellent bioavailability (>94%), it is 52 percent protein bound and has a low volume of distribution (10–20 liters). It reaches C-max within 2 hours after a single dose. As a result of multiple doses, both T-max and half-life increase. Due to the short half-life (2.5-5 h) of favipiravir, its hydroxylated form is rapidly eliminated through the kidneys. In addition to aldehyde oxidase, xanthine oxidase plays a marginal role in the elimination process. The pharmacokinetics of favipiravir is dose-dependent and time-dependent. The compound is not metabolized by cytochrome P-450, but it inhibits one of its components (CYP2C8). The medication should be used with caution when combined with drugs that are converted by CYP2C8 [13, 14]. Fig. (1) illustrates Favipiravir's intracellular activation.

Favipiravir has a novel mechanism of action in comparison to existing influenza antivirals that prevent the virus from entering and exiting cells [14]. As a result of its selective RNA inhibition properties, favipiravir-RTP inhibits RNA when activated. The polymerase prevents replication of the viral genome [15]. There is evidence that favipiravir-RTP interacts with RNA-dependent RNA polymerase (RdRp) under multiple hypotheses [16]. In spite of the fact that favipiravir was originally intended to treat influenza, the RdRp catalytic domain (favipiravir primary target) is expected to have similarities to other RNA viruses [9]. When the drug is administered into the body, it undergoes phosphoribosylation to become favipiravir-RTP. The following mechanisms are responsible for its antiviral effect:

A - This molecule serves as a substrate for RNA-dependent RNA polymerase (RdRp), which mistakes it for a purine nucleotide [7], thus inhibiting its activity.

B - The RNA strand is incorporated into the viral strand, preventing further expansion of the virus. Several RNA viruses retain the catalytic domain of the RdRp enzyme, allowing this drug to have a broad spectrum of activity.

According to recent findings, favipiravir causes lethal mutations during influenza virus infection in vitro [17]. Similar activity has not yet been demonstrated against SARS-CoV-2. Figs. (1 and 2) show Favipiravir's overall mechanism of action in its active and inactive forms, as well as how it interacts with the body's cell surface. In Fig. (2), we see a more detailed demonstration of how the drug interacts with living organisms.

Fig. (1). Favipiravir's mechanism of action and intracellular activation are illustrated.

Fig. (2). An overview of the mechanism of action of favipiravir.

There are several RNA viruses that are resistant to favipiravir.

Despite its adverse effects, favipiravir is generally considered safe, as confirmed by a large systematic review [23]. Here are some brief details about this drug's adverse effects. It is associated with an increase in total uric acid in the blood, diarrhea, a decreased white blood cell count (neutrophils), higher liver enzyme levels, and higher triglyceride levels in the blood.

• Symptoms of diarrhea
• Elevated uric acid levels (hyperuricemia).
• Neutrophil count reduced
• Having nausea
• Ingestion of vomit
• Pain in the abdomen

We are all aware of the risks associated with each drug. However, any drug should be used only if it has a minimal number of adverse effects and a high therapeutic effect. According to Table 3 , some adverse effects of favipiravir are minor, negligible, or less severe. Based on a large systematic review, this drug is effective in treating COVID-19 and safe in treating antiviral infections.

The COVID-19 infection is unlikely to disappear in the near future. Multiple clinical trials have been conducted on favipiravir against the devastating SARS-CoV-2 virus because of its novel antiviral activity and broad spectrum of activity. A recent study suggests that favipiravir can minimize viral clearance time and improve chest symptoms. The drug is considered relatively safe when used for a short period of time. Aside from being administered orally, in symptomatic patients not sick enough to require hospitalization, favipiravir is preferred. Due to the fact that most COVID-19 patients (85%) have mild to moderate disease and can be treated at home, this drug could potentially be beneficial for many patients. Additionally, favipiravir is being studied in combination with umifenovir to see if they complement one another or act synergistically [22, 23]. As for the side effects of the drug, asymptomatic hyperuricemia and slight, reversible elevations in transaminases are reported most frequently. Consequently, Favipiravir appears to be effective in treating mild to moderate symptoms associated with SARS-CoV-2 infection. A comprehensive review of the antiviral research conducted over the course of the last decade describes how favipiravir has shown to be experimentally useful against COVID-19 and describes how it has been compared to other antiviral drugs. It is possible to clarify the antiviral properties of this drug using bioinformatics databases and tools. Clinical and experimental studies have demonstrated that this drug can cure COVID-19 disease.