RdRp is an attractive target for developing therapies for COVID-19 as it plays a crucial role in the replication of SARS-CoV-2 (Scheme 1) and is well conserved between coronaviruses (RNA viruses). The multi-domain proteins contain less than 500 units of amino acids in length. The protein looks like a human cupped right hand with three subfolded domains constituting thumb, palm, and fingers. There is no known equivalent of RdRp in humans and it therefore produces no off-target untoward effects, making RdRp a selective target to develop RdRp inhibitors. Further, the availability of biochemical assays accelerates the development of RdRp inhibitors [12,13,14,15,16]. Two RdRp inhibitors, remdesivir (anti-Ebola virus experimental drug) [8] and favipiravir (anti-influenza drug) [9] have already been approved for COVID-19 treatment (Table 1). Both these broad-spectrum antiviral drugs have been shown to reduce the progression of COVID-19 and associated clinical symptoms along with a substantial decrease in recovery time [17,18,19]. Remdesivir is administered intravenously but many pharmaceutical companies are developing its acceptable and convenient oral dosage forms. On the other hand, favipiravir is an orally active antiviral drug but it shows a poor pharmacokinetic profile. Hence, some other possible RdRp inhibitors are being considered for COVID-19 treatment, which includes molnupiravir, galidesivir, ribavirin, sofosbuvir, and tenofovir [14,15]. Recently molnupiravir, an orally active RdRp inhibitor with a favorable pharmacokinetic profile, has received considerable attention owing to its ability to inhibit SARs-COV-2 replication, its quick clearance of SARs-COV-2, and the accompanying reduction in viral load and fast recovery time [20]. Molnupiravir reaches quantifiable concentration in 0.5 h between 600–1600 mg. Administration of a single dose produces mean C_max values up to 13.2 ng/mL and shows median t_max between 0.25 and 0.75 h and a biological half-life (t_{1/2 )}of 7 h. Its C_max and area under the plasma concentration versus time curve (AUC) increases in a dose-proportional manner with no accumulation following multiple doses suggesting that molnupiravir has no accumulative toxicity. Administration of molnupiravir in a fed state shows a slight decrease in the rate of absorption but no decrease in overall exposure. Furthermore, it exhibits fewer adverse reactions and good tolerability. Based on the pharmacokinetic profile of molnupiravir, it can be inferred that molnupiravir has a quick onset of action, a wide therapeutic window, and excellent tolerance with a good safety profile. These attributes make molnupiravir a very useful therapeutic molecule against COVID-19 [21].

Molnupiravir (MF: C₁₃H₁₉N₃O₇; MW: 329.31; CAS Registry Number: 2492423-29-5; Deleted CAS Registry Numbers: 2349386-89-4) is a pyrimidine ribonucleoside analog with a chemical name of ((2R,3S,4R,5R)-3,4-dihydroxy-5-(4-(hydroxyamino)-2-oxopyrimidin-1(2H)-yl) tetrahydrofuran-2-yl) methyl isobutyrate (Figure 1A). The other names of molnupiravir are EIDD-1931-isopropyl ester; EIDD-2801; MK-4482; uridine, 4-oxime, 5′-(2-methylpropanoate); and β-D-N4-hydroxycytidine-5′-isopropyl ester [21,22]. It is an orally active and directly acting antiviral interventional drug. Its efficacy and tolerability in COVID-19 patients has been investigated at doses of 200, 400, and 800 mg twice daily for five days.