Sofosbuvir for COVID‑19 Infection: a Potential Candidate

Letter to the Editor

Sofosbuvir for COVID‑19 infection: A potential candidate

Sir, biologically active triphosphate forms of sofosbuvir Severe acute respiratory syndrome (SARS) COV‑2 is following incorporation into enzyme, leading to currently ravaging the world and is associated with irreversibly blocked polymerase extension.[7] high morbidity and mortality. The absence of a clinically useful therapy or vaccine poses a severe challenge for In an in vitro study using a model for polymerase controlling this pandemic. extension, it was demonstrated that the activated form of sofosbuvir blocked further incorporation of nucleotides Coronaviruses, including SARS‑CoV‑2, are enveloped following incorporation into SARS‑CoV RdRp.[8] viruses. Genome of these virus particles consists of a Sofosbuvir does not affect host DNA‑polymerase. positive‑sense, single‑stranded RNA which has codes for structural proteins, nonstructural proteins (NSPs), With the worldwide availability of sofosbuvir, its and accessory proteins.[1] One of the critical proteins excellent safety profile, and preliminary studies is RNA‑dependent RNA polymerase (RdRp) which is suggesting its potential role in COVID‑19, there is an one of the NSPs (nsp12). Structural and phylogenetic urgent need to conduct control trials to test the efficacy analysis indicates that all known viral RdRps are and safety of this drug in patients with COVID‑19 highly conserved. Several drugs (e.g., favipiravir and disease. Use of this drug can potentially help in reducing remdesivir) bind to the RdRp active site and have the duration of viral shedding, reducing the progression demonstrated efficacy in vitro and animal models. of symptoms, and preventing the development of Recently, remdesivir has shown efficacy in decreasing the cytokine storm. disease duration in adult patients with severe COVID‑19 infection.[2] Financial support and sponsorship Nil. Sofosbuvir is an anti‑viral drug with activity against positive‑sense RNA virus. Infection with Conflicts of interest hepatitis C virus is its approved indication.[3] It is a There are no conflicts of interest. 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 Rohit Gupta, Puneet Dhamija phosphorylation within the host cell; this, in turn, Department of Gastroenterology and Pharmacology, AIIMS, terminates the replication of RNA in the nascent Rishikesh, Uttarakhand, India viral genome by acting as a defective substrate for Address for correspondence: [3] NS5B. Sofosbuvir has also been highly effective and Dr. Rohit Gupta, safe in patients suffering from hepatitis C infection[3] AIIMS, Rishikesh, Uttarakhand, India. and can be prescribed once daily due to its favorable E‑mail: [email protected] pharmacokinetic profile.[4] Submitted: 13-Jul-2020 Revised: 16-Jul-2020 Some preliminary studies have recently been conducted, Accepted: 24‑Jul‑2020 Published: 04-Aug-2020 in vitro, to explore the possible role of sofosbuvir in inhibiting RdRp of SARS‑CoV‑2.[5] In a recent study References by Elfiky,[6] the author built a COVID‑19 RdRp model 1. Bafna K, Krug RM, Gaetano M. Structural similarity of SARS‑CoV2 using homology modeling and sequence analysis. Mpro and HCV NS3/4A proteases suggest new approaches for Molecular docking was performed for antipolymerase identifying existing drugs useful as COVID‑19 therapeutics. drugs, including sofosbuvir and remdesivir. The results ChemRxiv Preprint 2020. doi: 10.26434/chemrxiv.12153615. suggested that sofosbuvir could tightly bind to the 2. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS. RdRp. Remdesivir for the Treatment of Covid-19 - Preliminary Report [published online ahead of print, 2020 May 22]. N Engl J Med. 2020; NEJMoa2007764. In another study, Chien et al. demonstrated that RdRp 3. Rodríguez‑Torres M. Sofosbuvir (GS‑7977), a pan‑genotype, of SARS‑CoV‑2 is also permanently blocked by the direct‑acting antiviral for hepatitis C virus infection. Expert Rev

Anti Infect Ther 2013;11:1269‑79. This is an open access journal, and articles are distributed under the terms 4. Mariño Z, van Bömmel F, Forns X, Berg T. New concepts of of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 sofosbuvir‑based treatment regimens in patients with hepatitis License, which allows others to remix, tweak, and build upon the work C. Gut 2014;63:207‑15. non‑commercially, as long as appropriate credit is given and the new creations 5. Sayad B, Sobhani M, Khodarahmi R. Sofosbuvir as repurposed are licensed under the identical terms. 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. Access this article online 6. Elfiky AA. Anti‑HCV, nucleotide inhibitors, re‑purposing against Quick Response Code: COVID‑19. Life Sci 2020;248:117477. doi:10.1016/j.lfs.2020.117477. Website: 7. Chien M, Anderson TK, Jockusch S, Tao C, Kumar S, Li X, et al. www.ijp‑online.com Nucleotide Analogues as Inhibitors of SARS‑CoV‑2 Polymerase. bioRxiv 2020. doi: https://doi.org/10.1101/2020.03.18.997585. 8. Ju J, Li X, Kumar S, Li X, Jockusch S, Chein M, et al. Nucleotide DOI: analogues as inhibitors of viral polymerases. bioRXiv 2020. doi: 10.4103/ijp.IJP_675_20 https://doi.org/10.1101/2020.03.12.989186.

How to cite this article: Gupta R, Dhamija P. Sofosbuvir for COVID‑19 infection: A potential candidate. Indian J Pharmacol 2020;52:232-3 © 2020 Indian Journal of Pharmacology Published by Wolters Kluwer - Medknow

Indian Journal of Pharmacology - Volume 52, Issue 3, May-June 2020 233