Letter to the Editor Open Access
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Virol. Sep 25, 2022; 11(5): 391-393
Published online Sep 25, 2022. doi: 10.5501/wjv.v11.i5.391
Possible agent for COVID-19 treatment: Rifampicin
Ozlem Celik Aydin, Department of Medical Pharmacology, Erzincan University, Mengucek Gazi Education and Research Hospital, Erzincan 24100, Turkey
Sonay Aydın, Sureyya Barun, Department of Pharmacology, Gazi University, Ankara 06500, Turkey
Sonay Aydın, Department of Radiology, Erzincan University, Erzincan 24100, Turkey
ORCID number: Ozlem Celik Aydin (0000-0002-8287-7126); Sonay Aydın (0000-0002-3812-6333); Sureyya Barun (0000-0003-3726-8177).
Author contributions: Aydın S, Aydin OC and Barun S conceived the study; Aydın S, Aydin OC and Barun S were responsible for designing, materials and supervision; Aydın S, Aydin OC and Barun S did the literature search, wrote the manuscript, and reviewed the manuscript critically; All authors have read and approved the final manuscript.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ozlem Celik Aydin, MD, Doctor, Department of Medical Pharma-cology, Erzincan University, Mengucek Gazi Education and Research Hospital, Başbağlar Mahallesi Hacı Ali Akın Caddesi No. 32 Erzincan/Merkez, Erzincan 24100, Turkey. ozlemclk_89@hotmail.com
Received: April 20, 2022
Peer-review started: April 20, 2022
First decision: June 8, 2022
Revised: June 20, 2022
Accepted: August 25, 2022
Article in press: August 25, 2022
Published online: September 25, 2022
Processing time: 156 Days and 14.6 Hours

Abstract

Rifampicin is a promising drug for the treatment of coronavirus disease 2019 based on its antiviral properties and recent in silico studies. In silico studies can serve as a foundation for further studies.

Key Words: Rifampicin; COVID-19; Treatment; In silico; Drug-drug interaction; Therapeutic potential

Core Tip: Rifampicin may be used as a treatment for coronavirus disease 2019 (COVID-19). Although it has a variety of drug-drug interactions, none of the important ones for the currently utilised COVID-19 medicines, favipiravir, enoxaparin, and aspirin, have been defined.



TO THE EDITOR

We read the review written by Panayiotakopoulos and Papadimitriou[1] with interest. The impacts of the coronavirus disease 2019 (COVID-19) pandemic are still being felt, and research into this topic continues due to the lack of a precise therapy. It is feasible to repurpose medications already used for other reasons for the treatment of COVID-19. The authors discussed rifampicin’s antiviral capabilities, its potential effects in computer simulations, its safety, and its role in clinical practice. Rifampicin is an antibacterial drug that inhibits DNA-dependent RNA polymerase in Mycobacterium tuberculosis, and its antiviral effect has been shown on some viruses[2]. On this basis, the potential efficacy of rifampicin as a COVID-19 treatment drug has been demonstrated in in silico research[3]. We concur with the authors’ suggestion for more research into the potential use of rifampicin for COVID-19.

In a study in which 20 United States Food and Drug Administration (FDA)-approved drugs were screened by molecular docking method in a possible drug design for COVID-19, rifampicin showed in silico binding to more than one target protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Other macrocyclic antibiotics showing binding are polymyxin B and bafilomycin A[4]. In another in silico study of FDA-approved drugs to treat COVID-19 infection, rifampicin has stronger binding affinity for the COVID-19 main protease Mpro[5]. However, additional studies are needed for validation.

Due to the properties of rifampicin, various drug-drug interactions (DDIs) may occur during its possible use. Rifampicin promotes the expression of cytochrome p450 3A4 (CYP3A4) in the small intestine and liver, as noted in the review. Additionally, according to the work by Panayiotakopoulos and Papadimitriou[1], an essential feature of rifampicin is that it activates proteins such as the P glycoprotein (P-gp) drug transporter and CYP2C-mediated metabolism[6]. There are possible DDIs with drugs used for the treatment of COVID-19 and for additional diseases. Favipiravir is one of the antiviral medications used for the treatment of COVID-19. It is metabolized mostly via aldehyde oxidase and xanthine oxidase[7], and the probability of a pharmacological interaction between rifampicin and favipiravir is low. Lopinavir and ritonavir are two additional widely used antivirals; coadministration of these drugs with rifampin may result in a decrease in the plasma concentrations of ritonavir and lopinavir due to rifampin’s induction of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of ritonavir and lopinavir[8]. Remdesivir is widely used for COVID-19 treatment, which is metabolized through hydrolysis reaction to its triphosphate active form via by carboxylesterase 1 (80%), cathepsin A (10%), and CYP3A (10%). Since rifampicin is a potential inductor of CYP3A4, concomitant administration might increase the metabolism of remdesivir[9]. Dexamethasone has a strong anti-inflammatory impact and is typically used as an adjunctive treatment for COVID-19 pneumonia. Rifampin may increase corticosteroid hepatic metabolism, hence diminishing their therapeutic impact. Corticosteroids’ half-life of elimination is shortened by up to 45% when co-administered with rifampin[10,11].

It has been suggested that prophylaxis of thrombosis in COVID-19 should include both anticoagulant and antiplatelet medications. Enoxaparin and aspirin are the two most often used anticoagulant and antiplatelet medications[12]. Fortunately, no significant medication interactions between these drugs and rifampicin have been identified. Apixaban and other direct oral anticoagulants can also be utilised. Rifampicin coadministration significantly increased apixaban plasma concentrations. When used orally, approximately 15% of apixaban is metabolised by CYP3A and roughly 6% by CYP1A2 and CYP2J2. The balance (50%) is eliminated unaltered in the form of faeces and urine. A single dose of rifampicin decreased apixaban clearance by 25%. Rifampicin largely influences apixaban absorption (and/or distribution), which could be attributed to an impairment of intestinal P-gp[13].

The authors said that rifampicin has been shown to be quite effective in treating COVID-19 in in silico tests. Additionally, multiple medication classes have been examined in silico for the treatment of COVID-19. Melatonin, ramelteon, and agomelatine, for example, have been demonstrated to significantly limit virus entry into cells in investigations. Ramelteon was proven to be the most effective antiviral against SARS-CoV-2[14].

Footnotes

Provenance and peer review: Unsolicited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Pharmacology and pharmacy

Country/Territory of origin: Turkey

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): 0

Grade C (Good): C

Grade D (Fair): D

Grade E (Poor): 0

P-Reviewer: Gupta S, United States; Varshney K, Australia S-Editor: Gong ZM L-Editor: Filipodia P-Editor: Gong ZM

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