Glycopeptides as Potential Interventions for COVID-19
Desalegn Getnet Demsie1, Abadi Kahsu Gebre2, Ebrahim M Yimer3
1Adigrat University, College of Medicine and Health Sciences, Department of Pharmacy, Adigrat, Ethiopia.
Insights
Glycopeptides and teicoplanin show promise in treating severe COVID-19 by inhibiting SARS-CoV-2 entry and replication. These drugs, repurposed from antibacterial use, offer a potential intervention against the novel coronavirus disease 2019 (COVID-19).
Area of Science:
- Virology and Infectious Diseases
- Pharmacology and Drug Repurposing
- Molecular Biology
Background:
- Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, primarily affects the pulmonary system and has led to a global health crisis.
- Currently, no specific vaccine or antiviral treatment exists for COVID-19, necessitating the exploration of alternative therapeutic strategies.
- Drug repurposing presents a viable approach to rapidly identify potential treatments for emerging viral infections like SARS-CoV-2.
Purpose of the Study:
- To review the antiviral activity of glycopeptides against coronaviruses, with a specific focus on SARS-CoV-2.
- To elucidate the potential mechanisms of action of glycopeptides in inhibiting SARS-CoV-2.
- To explore the clinical applications and potential of glycopeptides as a therapeutic intervention for COVID-19.
Main Methods:
- Review of existing literature on glycopeptide activity against viral infections, including SARS-CoV and MERS-CoV.
- Analysis of in vitro studies demonstrating the efficacy of glycopeptide derivatives and teicoplanin against SARS-CoV-2.
- Examination of proposed molecular mechanisms, including inhibition of viral entry and polyprotein processing.
Main Results:
- Glycopeptides, particularly aglycon derivatives and teicoplanin, exhibit significant in vitro activity against SARS-CoV-2.
- These compounds demonstrate low toxicity to human cell lines and inhibit viral entry and replication.
- Teicoplanin has been associated with complete viral clearance in patients with severe COVID-19 symptoms.
Conclusions:
- Glycopeptides and teicoplanin represent promising candidates for repurposing as antiviral agents against SARS-CoV-2.
- Their mechanism involves blocking key viral processes such as polyprotein processing, essential for viral replication.
- Further clinical investigation is warranted to establish the efficacy and safety of these agents in treating COVID-19.
Abstract:
Coronavirus disease 2019 (COVID-19), an infectious disease that primarily attacks the human pulmonary system, is caused by a viral strain called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak emerged from Wuhan, China, and later spread throughout the world. Until the first week of May 2020, over 3.7 million cases had been reported worldwide and more than 258,000 had died due to the disease. So far, off label use of various drugs has been tried in many clinical settings, however, at present, there is no vaccine or antiviral treatment for human and animal coronaviruses. Therefore, repurposing of the available drugs may be promising to control emerging infections of SARS-COV2; however, new interventions are likely to require months to years to develop. Glycopeptides, which are active against gram-positive bacteria, have demonstrated significant activity against viral infections including SARS-COV and MERS-COV and have a high resemblance of sequence homology with SARS-COV2. Recent in vitro studies have also shown promising activities of aglycon derivative of glycopeptides and teicoplanin against SARS-COV2. Hydrophobic aglycon derivatives and teicoplanin, with minimal toxicity to human cell lines, inhibit entry and replication of SARS-COV2. These drugs block proteolysis of polyprotein a/b with replicase and transcription domains. Teicoplanin use was associated with complete viral clearance in a cohort of patients with severe COVID-19 symptoms. This review attempts to describe the activity, elucidate the possible mechanisms and potential clinical applications of existing glycopeptides against corona viruses, specifically SARS-COV2.
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