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Vol 1 | Issue 3 | Oct - Dec 2022                                                                                       Indian J Pharm Drug Studies | 73 

Review Article   

Molnupiravir and Favipiravir in the therapeutics of SARS-CoV-2 - A 

review   

Ayush Singh1, 2, Riya Sehgal1, Karamjit Kaur1, Manju1, Jatin Isher1, 3, Neeru Kumari1, 4  

From, 1Department of Pharmacy, Global Group of Institutes, 2Department of Production, Alkem Laboratories Limited, Baddi, Solan, 

Himachal Pradesh,  3Department of Quality Assurance, Kwality Pharmaceuticals Ltd., 4Department of Quality Control, Kwality 

Pharmaceuticals Ltd., Amritsar, Punjab, India  

Correspondence to: Ayush Singh, Department of Production,  Alkem Laboratories Limited, Baddi, Solan, Himachal Pradesh - 173205 

and Department of Pharmacy, Global Group of Institutes, Amritsar, Punjab, India-143501. Email: ayushsingh28659@gmail.com  

ABSTRACT 

SARS-CoV-2 led to several unwanted deaths all across the globe since 2020. High mortality rates are seen by this virus. As per the 

various theories, numerous variant and deadly strains are come into existence in the world due to COVID-19 pandemic. To treat deadly 

strains of this virus, various anti-viral are drugs that are utilized in the therapeutics of COVID-19. Few antivirals are molnupiravir, 

favipiravir, remdesivir, alisopirivir and many more. Molnupiravir was originally developed to treat influenza at Emory University but 

also reports abandoned for mutagenicity concerns. Favipiravir is a prodrug has been approved to treat the influenza rather than the 

seasonal influenza and this medication selectively inhibition of RdRp. This review generally covers the two potent oral antiviral 

molnupiravir and favipiravir investigation. 

Key words: Molnupiravir, Favipiravir, COVID-19, SARS-CoV-2, Clinical data, Chemical. 

oronavirus disease 2019 (COVID-19), the illness 

caused by severe acute respiratory syndrome 

coronavirus 2 (SARS-CoV-2), has had a devastating 

effect on the world’s population resulting in more than 5.4 

million deaths worldwide and emerging as the most significant 

global health crisis since the influenza pandemic of 1918. Since 

being declared a global pandemic by the World Health 

Organization (WHO) on March 11, 2020, the virus continues to 

cause devastation, with many countries continuing to endure 

multiple waves of outbreaks of this viral illness [1]. COVID-19 

outbreak in China, led to tremendous breakdown in the 

healthcare sector. With emerging therapies including vaccines 

and anti-viral therapies, it is necessary to research on their 

clinical effects on treatment. Most of the drugs used in clinical 

practice have limited clinical experience [2].  

With the vast expanding knowledge of the SARs-CoV-2 

virology, newer potential targets are being identified. We have 

summarized the clinical picture of two anti-virals Molnuoiravir 

and Favipiravir. Molunipiravir is the first oral antiviral 

medicine to show considerable and convincing antiviral activity 

in vitro and in animal models. Shreds of evidence suggest that 

molnupiravir reduces hospitalization and mortality among 

unvaccinated individuals [3]. Favipiravir is also one such drug 

with a crucial role in treating mild to moderate COVID-19. 

With its oral form it can be easily administered and meant for 

treatment in mildly ill COVID-19 patients [4]. 

Variants of SARS-CoV-2   

Since the COVID-19 pandemic first began in December 2019, 

the severe acute respiratory syndrome coronavirus 2 (SARS-

CoV-2) virus has continuously evolved with many variants 

emerging across the world. These variants are categorized as 

the variant of interest (VOI), variant of concern (VOC), and 

variant under monitoring (VUM). As of September 15, 2021, 

there are four SARS-CoV-2 lineages designated as the VOC 

(alpha, beta, gamma, and delta variants). VOCs have increased 

transmissibility compared to the original virus, and have the 

potential for increasing disease severity [5]. All the variant of 

SARSCoV-2 are enlisted in the Table No. 1.  

Molnupiravir 

Molnupiravir is the drug that came into existence worldwide for 

the treatment of COVID-19. Molnupiravir (Emory Institute of 

Drug Development-2801 [EIDD-2801]/MK-4482) is one of the 

upcoming oral drugs which is promising. This oral agent was 

developed by Drug Innovation Ventures at Emory University, 

and later acquired by Ridgeback therapeutics in 

partnershipwith Merck & Co, USA. In general, antiviral drugs 

tested so far usually terminate the elongation of RNA-chain by 

targeting the viral polymerases but such anti-virals have not 

shown a very promising role in the treatment of SARS-CoV-2 

C 



Singh et al.                                                                                                 Molnupiravir and Favipiravir in SARS-CoV-2 

Vol 1 | Issue 3 | Oct - Dec 2022                                                                                        Indian J Pharm Drug Studies | 74  

infections [14]. This drug affects the RNA-dependent RNA-

Polymerase enzyme used by the coronavirus for transcription 

and replication of its viral RNA genome [15]. 

 

Figure 1: Chemical Structure of Molnupiravir 

Molnupiravir is an isopropyl ester prodrug of the nucleoside   

analogue β-d-N4–hydroxycytidine (NHC or EIDD-1931). 

Molnupiravir interferes with the replication of various viruses, 

including SARS-CoV-2. It inhibits SARS-CoV-2 replication in 

human lung tissue, blocks SARS-CoV-2 transmission in ferrets 

and reduces SARS-CoV-2 RNA in patients [15].It is β-D-N4-

hydroxycytidine (EIDD-1931) is an orally bioavailable 

ribonucleoside analogue and has broad-spectrum activity 

against numerous RNA viruses in animal models [16-18]. 

Molnupiravir (EIDD-2801), is a prodrug of β-D-N4-

hydroxycytidine (EIDD-1931) and is rapidly converted into 

EIDD-1931 in the plasma by the host’s esterase. After entering 

host cells, EIDD-1931 is intracellularly transformed into its 

active form, β-D-N4-hydroxycytidine-triphosphate, which 

inhibits viral replication through its incorporation into the viral 

genome. Consequently, the accumulation of mutations results 

in the viral error catastrophe. 

Mechanism of action 

Previously, it was developed to treat influenza and was 

recognized as another candidate for antiviral drugs. 

Understanding the mechanism of molnupiravir at the molecular 

level is critical to the further development of antiviral drugs. 

The drug is activated through metabolism in the body. Once 

inside the cell, it becomes an RNA-like component. In the first 

step, RNA polymerase incorporates these components into the 

RNA genome of the virus. In the next step, RNA-like 

components are paired with viral genetic material components.  

Viral RNA contains several mutations when it multiplies to 

produce new viruses, preventing the reproduction of the 

pathogen. This viral drug causes mutations in other RNA 

viruses and prevents them from expanding. Molnupiravir, a 

promising drug, is in the third phase of studies. When 

molnupiravir enters the cell, the active molnupiravir forms N-

hydroxycytidine hydrate (NHC triphosphate (MTP), which can 

be replaced by CTP or UTP by RdRp of SARS-CoV-2. 

Initially, when RdRp uses positive-strand genomic RNA for 

the synthesis sub-genomic RNA and negative-strand genomic 

RNA as a template, it regularly substitutes M for U or C. In the 

next step, +gRNA or +sgmRNA can be used   from RNA 

including M as a template. Then mutations are formed in 

positive-stranded genomic RNA products due to the presence 

of M in negative strand genomic RNA, and these products 

prevent the formation of healthy new viruses.  

At the end of this two-step mechanism, the mechanism of 

molnupiravir and its activated type were shownto result in RNA 

mutations through polymerases of other viruses. According to 

previous studies, molnupiravir-induced lethal mutagenesis was 

determined by a relatively high selectivity of MTP for 

incorporation as a CTP analogue and the indiscriminate 

incorporation of either ATP or GTP when MNP is centralized 

in the template strand [19]. 

Favipiravir 

Favipiravir (6-fluoro-3-hydroxypyrazine-2-carboxamine) 

which is a prodrug, is an anti-influenza drug that has shown 

broad-spectrum antiviral activity against a variety of other 

RNA viruses. This antiviral drug metabolized intracellularly 

into its active ribonucleoside 5′-triphosphate form that acts as a 

nucleotide analogue to selectively inhibit RdRp and induce   

lethal   mutagenesis.      Recently,   several   studies reported in 

vitro inhibitory activity of favipiravir against SARS-CoV-2 

with 50% EC50. Based on these results, more than 20 clinical 

trials on the management of COVID-19 by favipiravir are 

ongoing. 

Table 1: Variant of SARS-CoV-2 

VARIANT  STRAIN  DESCRIPTION  REFERENCES  

VOC  Alpha  Detected in Oct 2020 and correlated with a significant increase in the rate of COVID-

19 infection.    

[11]  

VOC  Beta  Detected in 18 December 2020 in South Africa.  [12]  

VOC  Gamma  Detected in Tokyo on 6 January 2021 by National Institutes of Infectious Diseases   [13]  

VOC  Delta   Detected in 6 May 2021 and it is globally dominant variant  [14]  

VOC  Omicron   Detected in 26 November 2021 in South Africa.  [15,16]  

VOI  Lambda  Detected in Peru in August 2020  [17]  

VOI  Mu  Detected in Colombia in January 2021.  [18]  



Singh et al.                                                                                                 Molnupiravir and Favipiravir in SARS-CoV-2 

Vol 1 | Issue 3 | Oct - Dec 2022                                                                                       Indian J Pharm Drug Studies | 75  

 

                                                                                                                                                                                                                                                                                                                                                                                                                            

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 4(b): Mechanism of action of Favipiravir (Favipiravir-RMP phosphorylates and produce Favipiravir-RTP in active 

form) 

Table 2 - Miscellaneous Anti-viral drugs used in the treatment of Covid-19 and their respective deadly strains  

Drug  Structure  Mechanism of Action  

Remdesivir  

 

The active metabolite of this drug interferes with the action of RdRp and 

evades profeeding by viral exoribonucleaases causing a reduction in the 

synthesis of RNA  

Alisopirivir/  

Debio 025/  

UNIL-025  

 

Abolish cyclophilin A or rotamase A  

  

  

Figure 2: Mechanism of action of Molnupiravir   Fig 3: Chemical Structure of Favipiravir 

   

  
Figure 4 (a): Mechanism of Favipiravir   

  



Singh et al.                                                                                                 Molnupiravir and Favipiravir in SARS-CoV-2 

Vol 1 | Issue 3 | Oct - Dec 2022                                                                                        Indian J Pharm Drug Studies | 76  

Umifenovir  

 

It suppress the membrane fusion of influenza virus and orifice impinging 

betwixt the virus and target host cell.  

Galidesivir/  

BCX4430/  

Immucillin-

A  

  

This is under Phase 1 human trail in Brazil for SARS-CoV-2 and possess 

broad spectrum antiviral potency against virus belongs to RNA families 

involving Bunyaviruses, Marburg virus disease, Zika virus, Ebola virus, 

Arenaviruses, Flaviviruses, Phleboviruses, Paramyxoviruses  

Nelfinavir    

 

This medication is a competitive inhibitor and protease inhibitor with 

activity against HIV-1.  

Lopinavir  

 

This drug also inhibit the HIV protease enzyme by producing an enzyme 

inhibitor complex, thus preventing the segmentation of the gag-pol 

polyproteins  

Ritonavir  
 

Generally, this medication abolishes the HIV viral proteinase enzyme that 

normally breaks the structural and replicative proteins that arises from 

major HIV genes.  

Table 3: clinical trial of several medications that are utilized in the therapeutics of SARS-CoV-2  

 Identifier number Drug Sponsor Sponsor Status Enrollment 

NCT04323527  Chloroquine 

Diphosphate  

Fundação de Medicina Tropical Dr. Heitor Vieira 

Dourado  

Completed  278  

NCT04343729  Methylprednisolone  Fundação de Medicina Tropical Dr. Heitor Vieira 

Dourado  

Completed  416  

NCT04853199  Quercetin  Hôpital Universitaire Sahloul  Recruiting  200  

NCT04334148  Hydroxychloroquine  Adrian Hernandez  Completed  1360  

NCT04510493  Canakinumab  University Hospital, Basel, Switzerland  Completed  116  

NCT04842747  VERU-111  Veru Inc.  Recruiting  300  

NCT04602000  CT-P59  Celltrion  Completed  1642  

NCT04978025  Colloidal silver  Hôpital Universitaire Sahloul  Recruiting  50  

NCT04646044  Bempegaldesleukin  Nektar Therapeutics  Completed  30  

NCT04560231  Remdesivir  Lahore General Hospital  Recruiting  30  



Singh et al.                                                                                                 Molnupiravir and Favipiravir in SARS-CoV-2 

Vol 1 | Issue 3 | Oct - Dec 2022                                                                                       Indian J Pharm Drug Studies | 77  

NCT04477993  Ruxolitinib  Vanderson Geraldo Rocha  Terminated  5  

NCT04780581  Dexamethasone  Fundación Instituto de Estudios de Ciencias de la 

Salud de Castilla y León  

Recruiting  290  

NCT04406246  Nitazoxanide  Materno-Perinatal Hospital of the State of Mexico  Completed  150  

NCT04473274  Pioglitazone  Samaritan Health Services  Completed  10  

NCT04668209  CX4549  University of Arizona  Recruiting  40  

NCT04414618  Opaganib  RedHill Biopharma Limited  Completed  42  

NCT04409509  CSL312  CSL Behring  Completed  124  

NCT04341116  TJ003234  I-Mab Biopharma Co. Ltd.  Recruiting  384  

NCT04632381  Zotatifin  Effector Therapeutics  Recruiting  36  

NCT04672564  Carrimycin  Shenyang Tonglian Group CO., Ltd  Recruiting  300  
 
Mechanism of action  

Favipiravir-RTP binds to and inhibits RdRp, which ultimately 

prevents viral transcription and replication. Favipiravir is a 

purine base analogue that is converted to active favipiravir-RTP 

by intracellular phosphoribosylation. It is a selective and potent 

inhibitor of RdRp of RNA viruses. Favipiravir is incorporated 

into the nascent viral RNA by error-prone viral RdRp, which 

leads to chain termination and viral mutagenesis [20]. 

The RdRp existing in various types of RNA viruses enables 

a broader spectrum of antiviral activities of favipiravir. After 

RNA viral incorporation, favipiravir-RTP works as a mutagen, 

which is capable of fleeing coronavirus repair machinery. The 

favipiravir-RTP adds to the pressure on CoV nucleotide 

content, which already has a low cytosine in the SARSCoV-2 

genome. In total, along with the increased frequency of 

mutation, favipiravir-RTP has a positive effect on SARSCoV-

2 by a cytopathic effect, which is induced by the virus, 

reduction in the number of viral RNA, and infectious particles. 

Favipiravir has a strong binding affinity to RdRp with a 

docking score of 6.925. Hence, targets the Achilles heel (RdRp 

complex) of SARS-CoV-2.  

Miscellaneous Anti-Viral agents in the therapeutics of 

SARS-CoV-2 

We have also elaborated the list of other drugs that are being 

employed in the treatment of COVID-19. There are several 

kinds   of   anti-viral   drugs   other   than   molnupiravir   and 

favipiravir for the treatment of COVID-19. 

Clinical data 

Major  drugs  that  are  under  clinical  trial  of various  drugs 

under   several   phases   for   the   development   of   new 

pharmaceutical  medicament  for  the  treatment  of  SARS-

CoV-2 from different genera (or different classes of drugs) are 

entitled in the Table 3. 

Conclusion and Future Scope 

The review concludes that antivirals used in the treatment of 

coronavirus can serve excellent in treatment. Anti-viral drugs 

prevent viral replication through several kinds of mechanisms 

or physiology. This review justifies that molnupiravir (MK-

4482) is a prodrug used to treat mild-to-moderate COVID-19. 

MK-4482 is the first oral, direct-acting antiviral that shows 

highly effective at reducing nasopharyngeal SARS-CoV-2 

infection. Favipiravir act as a prodrug and undergoes 

ribosylations and phosphorylation intracellularly to become 

active favipiravir-RTP. This drug inhibits RdRp at long last 

prevent viral transcription and replication. Both drugs are not 

preferred in pregnancy because several studies and evidence 

show that molnupiravir causes fetal harm. During clinical 

treatment, these newer generation drugs serve as a potential 

drug for the therapeutics of COVID-19. Intensive 

investigations related to antiviral drugs that are utilized in the 

therapeutics of SARS-CoV-2 for specific pharmacological 

actions, and their mechanism of action, safety, and efficacy 

could be the future research interest to explore the drugs 

exhaustively. There is still an ever-increasing need for high 

quality evidence to investigate newer and effective therapies for 

COVID-19. 

Abbrevatons 

+sgmRNA: Positive-strand Subgenomic   mRNA; ATP: 

Adenosine  triphosphate; CTP: Cytidine  triphosphate; EC: 

Effective  concentrations; EIDD: Emory  Institute  for  Drug 

Development; Favipiravir-RTP: Favipiravir ribofuranosyl-

5B-triphosphate; GTP: Guanosine-5’-triphosphate; HIV: 

Human    immunodeficiency    virus; RdRp: RNA-dependent  

RNA  polymerase; SARS-CoV-2: Severe Acute Respiratory 

Syndrome Corona virus 2; UTP: Uridine  triphosphate; VOC: 

Variant  of  Concern; VOI: Variant of Interest. 

REFERENCES 

1. Singh AK, Singh A, Singh R, et al. Molnupiravir in COVID-19: A 

systematic review of literature. Diabetes Metab Syndr [Internet]. 

2021; 15(6): 102329.  

2. Zarenezhad E, Marzi M.  Review on molnupiravir as a promising 

oral drug for the treatment of COVID-19. Med Chem Res 

[Internet].     2022; 31(2): 232-43.  

3. Kabinger F, Stiller C, Schmitzová J, et al. Mechanism of 

molnupiravir-induced SARS-CoV-2 mutagenesis. Nat Struct Mol 

Biol [Internet]. 2021; 28(9): 740-6.  



Singh et al.                                                                                                 Molnupiravir and Favipiravir in SARS-CoV-2 

Vol 1 | Issue 3 | Oct - Dec 2022                                                       Indian J Pharm Drug Studies | 78  

4. Baranovich T, Wong S-S, Armstrong J, et al. T-705 (favipiravir) 

induces lethal Mutagenesis in influenza A H1N1 virusesin vitro. J 

Virol [Internet]. 2013; 87(7): 3741-51.  

5. Reynard O, Nguyen X-N, Alazard-Dany N, et al.  Identification of 

a new ribonucleoside inhibitor of Ebola virus replication. Viruses 

[Internet]. 2015; 7(12): 6233-40.  

6. Toots M, Yoon J-J, Hart M, et al. Quantitative efficacy paradigms 

of the influenza clinical drug candidate EIDD-2801 in the ferret 

model. Transl Res [Internet]. 2020; 218: 16-28.  

7. Urakova N, Kuznetsova V, Crossman DK, et al.  Β-d -N4-

hydroxycytidine is a potent anti-alphaviru compound that induces 

a High Level of mutations in the viral genome. J Virol [Internet]. 

2018; 92(3).  

8. Painter, George R, Bluemling, et al. N4-hydroxycytidine and 

derivatives and anti-viral uses related there to published 2020-09-

03, assigned to Emory University. 

9. ClinicalTrials.gov NCT04405739. The Safety of Molnupiravir 

(EIDD-2801) and its Effect on Viral Shedding of SARS-CoV2 

(END-COVID) 

10. Clinicaltrails.gov NCT04402203. Study on Safety and Efficay of 

Favipiravir (Favipira) for COVID-19 Patient in selected Hospitals 

of Bangladesh. 

11. New evidence on VUI-2020/2021 and review of the public health 

risk assessment. 15 December 2020. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

12. Lowe D, “The new mutations” American Association for the 

Advancement of Science 22 December 2020. 

13. Faria NR, Claro IM, Candido D, et al, “Genomic Characterisation 

of an emergent SARS-CoV-2 lineage in Manaus: prelimary 

findings.March 2021.  

14. Cutler S. “Nepal variant”: what we’ve learned so far. The 

Conversation [Internet]. 2021 Jun 16 [cited 2022 15. Aug 1];  

15. Torjesen, Ingrid, 2021. COVID-19; Omicron may be more 

transmissible than other variants. 

16. Callaway, Ewen. Heavily mutated corona virus 2021. 

17. COVID-19 coronavirus: Ultra-contagious Lambda variant. 2021; 

6(7). 

18. O’Neill L. Mu: everything you need to know about the new 

coronavirus variant of interest. The Conversation [Internet].  
 
 

How to cite this article: Ayush Singh, Riya Sehgal, 

Karamjit Kaur, Manju, Jatin Isher, Neeru Kumari. 

Molnupiravir and Favipiravir in the therapeutics of SARS-

CoV-2 - A review. Indian J Pharm Dug Studies. 2022: 1(3) 

73-78. 

Funding: None                     Conflict of Interest: None Stated 

 


