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Year : 2020  |  Volume : 52  |  Issue : 3  |  Page : 232--233

Sofosbuvir for COVID-19 infection: A potential candidate

Rohit Gupta, Puneet Dhamija 
 Department of Gastroenterology and Pharmacology, AIIMS, Rishikesh, Uttarakhand, India

Correspondence Address:
Dr. Rohit Gupta
AIIMS, Rishikesh, Uttarakhand
India




How to cite this article:
Gupta R, Dhamija P. Sofosbuvir for COVID-19 infection: A potential candidate.Indian J Pharmacol 2020;52:232-233


How to cite this URL:
Gupta R, Dhamija P. Sofosbuvir for COVID-19 infection: A potential candidate. Indian J Pharmacol [serial online] 2020 [cited 2021 Nov 28 ];52:232-233
Available from: https://www.ijp-online.com/text.asp?2020/52/3/232/291392


Full Text



Sir,

Severe acute respiratory syndrome (SARS) COV-2 is currently ravaging the world and is associated with high morbidity and mortality. The absence of a clinically useful therapy or vaccine poses a severe challenge for controlling this pandemic.

Coronaviruses, including SARS-CoV-2, are enveloped viruses. Genome of these virus particles consists of a positive-sense, single-stranded RNA which has codes for structural proteins, nonstructural proteins (NSPs), and accessory proteins.[1] One of the critical proteins is RNA-dependent RNA polymerase (RdRp) which is one of the NSPs (nsp12). Structural and phylogenetic analysis indicates that all known viral RdRps are highly conserved. Several drugs (e.g., favipiravir and remdesivir) bind to the RdRp active site and have demonstrated efficacyin vitro and animal models. Recently, remdesivir has shown efficacy in decreasing the disease duration in adult patients with severe COVID-19 infection.[2]

Sofosbuvir is an anti-viral drug with activity against positive-sense RNA virus. Infection with hepatitis C virus is its approved indication.[3] It is a direct-acting antiviral agent and acts by inhibiting NS5B RdRp of this virus. This drug gets converted into an active form to nucleoside triphosphate after phosphorylation within the host cell; this, in turn, terminates the replication of RNA in the nascent viral genome by acting as a defective substrate for NS5B.[3] Sofosbuvir has also been highly effective and safe in patients suffering from hepatitis C infection[3] and can be prescribed once daily due to its favorable pharmacokinetic profile.[4]

Some preliminary studies have recently been conducted, in vitro, to explore the possible role of sofosbuvir in inhibiting RdRp of SARS-CoV-2.[5] In a recent study by Elfiky,[6] the author built a COVID-19 RdRp model using homology modeling and sequence analysis. Molecular docking was performed for antipolymerase drugs, including sofosbuvir and remdesivir. The results suggested that sofosbuvir could tightly bind to the RdRp.

In another study, Chien et al. demonstrated that RdRp of SARS-CoV-2 is also permanently blocked by the biologically active triphosphate forms of sofosbuvir following incorporation into enzyme, leading to irreversibly blocked polymerase extension.[7]

In anin vitro study using a model for polymerase extension, it was demonstrated that the activated form of sofosbuvir blocked further incorporation of nucleotides following incorporation into SARS-CoV RdRp.[8] Sofosbuvir does not affect host DNA-polymerase.

With the worldwide availability of sofosbuvir, its excellent safety profile, and preliminary studies suggesting its potential role in COVID-19, there is an urgent need to conduct control trials to test the efficacy and safety of this drug in patients with COVID-19 disease. Use of this drug can potentially help in reducing the duration of viral shedding, reducing the progression of symptoms, and preventing the development of cytokine storm.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Bafna K, Krug RM, Gaetano M. Structural similarity of SARS-CoV2 Mpro and HCV NS3/4A proteases suggest new approaches for identifying existing drugs useful as COVID-19 therapeutics. ChemRxiv Preprint 2020. doi: 10.26434/chemrxiv.12153615.
2Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS. Remdesivir for the Treatment of Covid-19 - Preliminary Report [published online ahead of print, 2020 May 22]. N Engl J Med. 2020; NEJMoa2007764.
3Rodríguez-Torres M. Sofosbuvir (GS-7977), a pan-genotype, direct-acting antiviral for hepatitis C virus infection. Expert Rev Anti Infect Ther 2013;11:1269-79.
4Mariño Z, van Bömmel F, Forns X, Berg T. New concepts of sofosbuvir-based treatment regimens in patients with hepatitis C. Gut 2014;63:207-15.
5Sayad B, Sobhani M, Khodarahmi R. Sofosbuvir as repurposed antiviral drug against COVID-19: Why were we convinced to evaluate the drug in a registered/approved clinical trial? Arch Med Res 2020. doi: 10.1016/j.arcmed.2020.04.018.
6Elfiky AA. Anti-HCV, nucleotide inhibitors, re-purposing against COVID-19. Life Sci 2020;248:117477. doi:10.1016/j.lfs.2020.117477.
7Chien M, Anderson TK, Jockusch S, Tao C, Kumar S, Li X, et al. Nucleotide Analogues as Inhibitors of SARS-CoV-2 Polymerase. bioRxiv 2020. doi: https://doi.org/10.1101/2020.03.18.997585.
8Ju J, Li X, Kumar S, Li X, Jockusch S, Chein M, et al. Nucleotide analogues as inhibitors of viral polymerases. bioRXiv 2020. doi: https://doi.org/10.1101/2020.03.12.989186.