ORTCID (Teicoplanin) as a Therapeutic Agent for COVID-19*
25.04.2021
ORTCID (Teicoplanin) as a Therapeutic Agent for COVID-19*
Given the ongoing search for effective medications to treat the novel coronavirus infection, significant attention from specialists is focused on antimicrobial drugs that, in addition to their activity against various prokaryotes, exhibit antiviral properties. One such drug is the glycopeptide antibiotic teicoplanin.
Teicoplanin (Ortcid) is a mixture of several compounds: five primary ones (which are named teicoplanin and numbered from A2-1 to A2-5) and four secondary ones (which are also named teicoplanin and numbered from RS-1 to RS-4). It has been used in clinical practice since the late 1980s.
Spectrum of antiviral activity in vitro
Teicoplanin (Ortcid) has antiviral potential against a variety of viruses, such as Ebola, influenza virus, flavivirus, hepatitis C virus, HIV, and coronaviruses MERS-CoV and SARS-CoV-1 and -2 [3, 11, 12, 13].
Mechanism of action on SARS-CoV-2
Teicoplanin (Ortcid) acts at the early stages of the virus lifecycle within the cell, inhibiting critical processes occurring in late endosomes (multivesicular bodies) [10, 11].
http://kraspharma.ru/images/u/sars-cov_2(1).jpg
Fig. 1. Target of teicoplanin action on SARS-CoV-2 (shown by the red arrow, explanation in the text).
Blocks the cleavage of the viral glycoprotein (GP) in the viral envelope by endosomal cysteine proteases (cathepsin L).
Prevents internalization and fusion of the viral envelope with the endosomal membrane.
Prevents the release of the nucleocapsid with viral RNA into the cytosol and halts viral replication.
Thus, teicoplanin (Ortcid) halts the process at the level of the primary infected cell and/or prevents further disease progression by localizing and stabilizing the process [10, 11]. Teicoplanin does not affect the immune system, making its application more predictable.
Secondary Infection Issue
The primary pathogens of "early" bacterial complications in the lungs during COVID-19 are Gram(+) cocci, against which teicoplanin demonstrates exceptional efficacy. Therefore, this drug, in addition to its antiviral effect, may also prevent and/or provide therapeutic benefits in cases of secondary bacterial infections.
Administration Method
Intravenously or intramuscularly.
Dosage Selection
The glycopeptide concentration required to inhibit 50% of viruses (IC50) in vitro is 1.66 µM, which is significantly lower than the concentrations achieved in plasma after administering 400 mg of teicoplanin per day (around 8.78 µM), or the therapeutic dose of the antibiotic [10]. Thus, a standard therapeutic dose is sufficient to achieve the antiviral effect and provide effective prevention or treatment of Gram(+) secondary lung infections.
Safety
In terms of safety and the risks of serious adverse reactions, teicoplanin (Ortcid) significantly outperforms other drugs indicated for SARS-CoV-2.
Generally, teicoplanin is well tolerated. Adverse reactions rarely require discontinuation of treatment and are mostly mild and transient; severe adverse reactions are rare.
Nephrotoxicity: The nephrotoxicity typically associated with glycopeptides, described as a complication during prolonged vancomycin use, is not observed with teicoplanin when used in standard therapeutic doses.
Ototoxicity: No ototoxic effects have been observed with teicoplanin.
Red-man syndrome: This syndrome has not been observed in volunteers receiving teicoplanin, and it is extremely rare in clinical practice (1 case in 2500 patients), even with rapid intravenous administration.
Local tolerance: Phlebitis with intravenous administration and pain with intramuscular injection are rare with teicoplanin.
Use During Pregnancy and Lactation
Teratogenic effects of the drug are absent. During pregnancy and lactation, it should only be used when the benefit to the mother outweighs the potential risk to the fetus or infant (considering that the drug is not absorbed in the gastrointestinal tract, including the portion that may pass into the infant's body via breast milk).
Thus, based on the available information, teicoplanin (Ortcid) could be considered as another potential alternative for the treatment of the novel coronavirus infection COVID-19.
References:
Teicoplanin (Ortcid) is a mixture of several compounds: five primary ones (which are named teicoplanin and numbered from A2-1 to A2-5) and four secondary ones (which are also named teicoplanin and numbered from RS-1 to RS-4). It has been used in clinical practice since the late 1980s.
Spectrum of antiviral activity in vitro
Teicoplanin (Ortcid) has antiviral potential against a variety of viruses, such as Ebola, influenza virus, flavivirus, hepatitis C virus, HIV, and coronaviruses MERS-CoV and SARS-CoV-1 and -2 [3, 11, 12, 13].
Mechanism of action on SARS-CoV-2
Teicoplanin (Ortcid) acts at the early stages of the virus lifecycle within the cell, inhibiting critical processes occurring in late endosomes (multivesicular bodies) [10, 11].
http://kraspharma.ru/images/u/sars-cov_2(1).jpg
Fig. 1. Target of teicoplanin action on SARS-CoV-2 (shown by the red arrow, explanation in the text).
Blocks the cleavage of the viral glycoprotein (GP) in the viral envelope by endosomal cysteine proteases (cathepsin L).
Prevents internalization and fusion of the viral envelope with the endosomal membrane.
Prevents the release of the nucleocapsid with viral RNA into the cytosol and halts viral replication.
Thus, teicoplanin (Ortcid) halts the process at the level of the primary infected cell and/or prevents further disease progression by localizing and stabilizing the process [10, 11]. Teicoplanin does not affect the immune system, making its application more predictable.
Secondary Infection Issue
The primary pathogens of "early" bacterial complications in the lungs during COVID-19 are Gram(+) cocci, against which teicoplanin demonstrates exceptional efficacy. Therefore, this drug, in addition to its antiviral effect, may also prevent and/or provide therapeutic benefits in cases of secondary bacterial infections.
Administration Method
Intravenously or intramuscularly.
Dosage Selection
The glycopeptide concentration required to inhibit 50% of viruses (IC50) in vitro is 1.66 µM, which is significantly lower than the concentrations achieved in plasma after administering 400 mg of teicoplanin per day (around 8.78 µM), or the therapeutic dose of the antibiotic [10]. Thus, a standard therapeutic dose is sufficient to achieve the antiviral effect and provide effective prevention or treatment of Gram(+) secondary lung infections.
Safety
In terms of safety and the risks of serious adverse reactions, teicoplanin (Ortcid) significantly outperforms other drugs indicated for SARS-CoV-2.
Generally, teicoplanin is well tolerated. Adverse reactions rarely require discontinuation of treatment and are mostly mild and transient; severe adverse reactions are rare.
Nephrotoxicity: The nephrotoxicity typically associated with glycopeptides, described as a complication during prolonged vancomycin use, is not observed with teicoplanin when used in standard therapeutic doses.
Ototoxicity: No ototoxic effects have been observed with teicoplanin.
Red-man syndrome: This syndrome has not been observed in volunteers receiving teicoplanin, and it is extremely rare in clinical practice (1 case in 2500 patients), even with rapid intravenous administration.
Local tolerance: Phlebitis with intravenous administration and pain with intramuscular injection are rare with teicoplanin.
Use During Pregnancy and Lactation
Teratogenic effects of the drug are absent. During pregnancy and lactation, it should only be used when the benefit to the mother outweighs the potential risk to the fetus or infant (considering that the drug is not absorbed in the gastrointestinal tract, including the portion that may pass into the infant's body via breast milk).
Thus, based on the available information, teicoplanin (Ortcid) could be considered as another potential alternative for the treatment of the novel coronavirus infection COVID-19.
References:
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- Baron SA, Devaux C, Colson P, Raoult D, Rolain JM. Teicoplanin: an alternative drug for the treatment of coronavirus COVID-19? Int J Antimicrob Agents. 2020 Mar 13:105944.
- Helal GK, Gad MA, Abd-Ellah MF, Eid MS. Hydroxychloroquine augments early virological response to pegylated interferon plus ribavirin in genotype-4 chronic hepatitis C patients. J Med Virol 2016;88(12):2170-8.
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- Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020. https://doi.org/10.1038/s41422- 020-0282-0.
- Colson P, Rolain JM, Raoult D. Chloroquine for the 2019 novel coronavirus. Int J Antimicrob Agents 2020 Feb 17. https://doi.org/10.1016/j.ijantimicag.2020.105923.
- Zhou N, Pan T, Zhang J, Li Q, Zhang X, Bai C, et al. Glycopeptide antibiotics potently inhibit cathepsin L in the late endosome/lysosome and block the entry of Ebola virus, middle east respiratory syndrome coronavirus (MERSCoV), and severe acute respiratory syndrome coronavirus (SARS-CoV). J Biol Chem 2016;291:9218-32.
- Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020 Feb 15;395(10223):497-506.
- Zhang J, Ma X, Yu F, Liu J, Zou F, Pan T, et al. Teicoplanin potently blocks the cell entry of 2019-nCoV. BioRxiv 2020:2020.02.05.935387.
- Zhou N, Pan T, Zhang J, Li Q, Zhang X, Bai C, et al. Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV). J Biol Chem 2016;291:9218–32.
- Colson P, Raoult D. Fighting viruses with antibiotics: an overlooked path. Int J Antimicrob Agents 2016;48:349–52.
- Pan T, Zhou N, Zhang H. USE OF TEICOPLANIN ANTI-MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS. WO/2016/201692, 2015.
- Giancarlo Ceccarelli, Francesco Alessandri, Gabriella d'Ettorre, Cristian Borrazzo, Ornella Spagnolello, Alessandra Oliva, Franco Ruberto, Claudio M. Mastroianni, Francesco Pugliese, Mario Venditti, Intensive Care COVID-19 Study Group of Sapienza University. Is teicoplanin a complementary treatment option for COVID-19? The question remains. Int J Antimicrob Agents. 2020 Aug; 56(2): 106029.
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