Considering the widespread use of topical ophthalmic drugs (artificial tears, anti-glaucoma drugs, topical antibiotics, etc.), it is interesting to investigate the possibility of a collateral antiviral action, which could explain the controversial data on the incidence of conjunctivitis, as well as represent a potential starting point for the treatment of SARS-CoV-2 on the ocular surface.
COVID-19 (COronaVIrus Disease 19), which has become pandemic in the last year, is currently the main global public health concern.
Several studies have described ocular involvement in COVID-19 infection and a potential role of the eye in SARS-CoV-2 transmission. Conjunctivitis may also be the first symptom of COVID-19, preceding the onset of cough and fever. The prevalence of conjunctivitis in patients with COVID-19 is, however, still controversial: some reports indicate a prevalence of only 0.9%, while others report that as many as 31.6% of hospitalised patients with severe COVID-19 have conjunctivitis.
Preservatives and excipients
Most eye drops and ophthalmic ointments also have some antimicrobial activity due to the presence of preservatives. Although an antiviral effect is theoretically possible with all the most commonly used preservatives, those that have so far demonstrated potential antiviral efficacy are: sodium perborate (and related hydrogen peroxide), stabilised complex oxychloride (Purite, an oxidising agent), citric acid, sodium bicarbonate and boric acid. These substances are, in fact, capable of destroying the lipid envelope of viruses: oxidants are capable of deactivating the intracellular enzymes of microbes and altering their nucleic acids, proteins and lipid components, while detergents damage cell membranes in a non-specific way.
Antiseptic-disinfectant agents
Given the lack of specific antiviral treatments for COVID-19, a more thorough understanding of the potential efficacy on viruses of antiseptic disinfectants is desirable. With regard to the formulations available for ophthalmic use, the most common and potentially interesting are those based on povidone iodine and sodium hypochlorite.
Artificial tears
The prevalence of dry eye syndrome in the general population varies from 5 to 50%, so artificial tears are probably among the most frequently used ophthalmic preparations by patients. Interestingly, a number of substances contained in these formulations have antiviral action. These include high molecular weight hyaluronic acid, trehalose, carbopol and lactoferrin, as well as chamomile oils or extracts of Echinacea purpurea, Rubus fruticosus, Aloe vera, Ginkgo biloba, Centella asiatica and Foeniculum vulgare. Other ingredients presumed to have a mild anti-viral action are glycerol, l-carnitine and ozonated oils.
Overall, artificial tears have been shown to exert their antiviral action by different mechanisms and on a wide range of DNA and/or RNA viruses. Several polymeric constituents and natural extracts have even been shown to inhibit certain viruses belonging to the Coronaviridae family. Furthermore, certain electrolytes, contained in artificial tears with the function of maintaining ocular surface homeostasis, can also have an antiviral effect. For example, zinc (0.25%), used as an excipient, has been shown to inhibit SARS-CoV-2 polymerase activity, blocking viral replication. Chloroquine has recently been used in artificial tears at a concentration of 0.03%, which has shown an inhibitory effect on viral replication of various viruses, including SARS-CoV-2.
Anti-glaucoma ophthalmic preparations
Some molecules used to treat glaucoma have been shown to influence the clinical course of viral infections. These include timolol maleate used in the treatment of herpes simplex infections and brinzolamide, which has the ability to inhibit the multiplication of H3N2, H1N1 influenza and H5N2 and H7N1 avian influenza viruses.
Antibiotics and other antimicrobials
A limited number of antibiotics contained in ophthalmic preparations also have antiviral activity. Categories of antibiotics with antiviral potential include macrolides (such as azithromycin, which has shown activity against SARS-CoV-2), tetracyclines (proposed in the treatment of COVID-19), fluoroquinolones, aminoglycosides, chloramphenicol and fusidic acid.
Anti-allergic and antihistamine ophthalmic preparations
It is estimated that about 20% of the world's population has an allergic disease, with ocular involvement in 60% of cases, in fact, among ophthalmic preparations those with anti-allergic action are the most widely used. Surprisingly, several antihistamines, such as chlorcyclizine, chlorpheniramine and diphenhydramine have demonstrated antiviral action against hepatitis C virus (HCV), filoviruses (Ebola virus, Marburg virus and Cuevavirus) and influenza A viruses.
Anti-inflammatory ophthalmic preparations
Another interesting category of active ingredients contained in ophthalmic preparations is that of anti-inflammatory agents. Generally, these eye drops, or ophthalmic ointments, are used to treat or prevent various types of ocular inflammation (e.g. during peri-surgery or for uveitis) or to control pain. Some NSAIDs (non-steroidal anti-inflammatory drugs) have shown antiviral action, e.g. on the herpes simplex virus (HSV).
Ophthalmic preparations thus represent a vast reservoir of potential drug candidates for repurposing as antiviral agents.Â
Bibliography:
Pietro Emanuele Napoli et al. A Panel of Broad-Spectrum Antivirals in Topical Ophthalmic Medications from the Drug Repurposing Approach during and after the Coronavirus Disease 2019 Era. J Clin Med. 2020 Aug; 9(8): 2441. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463888/
Dr. Carmelo Chines
Direttore responsabile
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