Algal Polysaccharides from Cladophora spp. as a Promising Anti-Herpes simplex virus (HSV) Agent

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Herpes simplex virus (HSV) is responsible for various human diseases, including fever blisters, genital herpes, and neonatal herpes. The search for effective treatments is ongoing due to the virus’s persistent nature and potential for severe health complications. Recent research has focused on natural substances as potential remedies, with particular interest in polysaccharide extracts from algae. This article delves into the promising antiviral properties of algal polysaccharides, specifically from Cladophora spp., and their potential application in combating HSV infections.

The Prevalence and Challenge of HSV

HSV is a prevalent infection worldwide, with HSV-1 primarily causing oral herpes and HSV-2 responsible for genital herpes. According to the World Health Organization (WHO), an estimated 3.7 billion people under 50 are infected with HSV-1, and 491 million people aged 15-49 are infected with HSV-2. These infections pose significant public health challenges due to their high transmission rates and lifelong persistence in the host​ ​.

Current Treatments and Limitations

Current HSV treatments, primarily nucleoside analogues like acyclovir, valacyclovir, penciclovir, and famciclovir, target viral DNA polymerase. However, these drugs often lead to side effects and the development of drug-resistant HSV strains due to mutations in viral thymidine kinase and DNA polymerase genes​. The increasing prevalence of drug-resistant HSV strains has fueled the search for alternative treatments.

Natural Substances as Antiviral Agents

Several natural substances have demonstrated antiviral properties, including polysaccharides, peptides, proteins, and phenolic compounds. These compounds can interfere with various stages of the viral life cycle, including entry, replication, and egression. Polysaccharides, particularly sulfated polysaccharides, have shown significant antiviral activity. These molecules are abundant in marine algae and have been studied for their potential to inhibit viral infections​ .

Algal Polysaccharides: Structure and Extraction

The structure of polysaccharides from Cladophora spp. includes sulfate groups, as identified by FT-IR spectroscopy. These sulfated polysaccharides are known for their strong antiviral activity. The extraction process often involves purification steps, such as ion exchange chromatography, to enhance the polysaccharide’s purity and antiviral efficacy​ ​.

Antiviral Activity of Cladophora spp. Polysaccharides

Studies have shown that polysaccharide extracts from Cladophora spp. exhibit low toxicity and significant antiviral activity against HSV-1 and HSV-2 in Vero cells. The effectiveness of these extracts varies depending on the timing of the treatment relative to viral adsorption. For instance, treatment with algal extract before and during viral adsorption shows higher antiviral efficacy compared to post-adsorption treatments​ .

The EC50 values for Cladophora spp. polysaccharides against HSV-1 were 70.31 µg/mL (before viral adsorption), 15.17 µg/mL (during viral adsorption), and >5000 µg/mL (after viral adsorption). For HSV-2, the EC50 values were 5.85 µg/mL (before viral adsorption), 2.57 µg/mL (during viral adsorption), and >5000 µg/mL (after viral adsorption)​​. These values indicate that the algal polysaccharides are more effective during the early stages of viral infection.

Comparison with Other Algal Polysaccharides

The antiviral activity of Cladophora spp. polysaccharides is comparable to other algal extracts. For example, polysaccharides from Monostroma nitidum, Caulerpa brachypus, and Sargassum muticum have also shown potent anti-HSV activities, with EC50 values ranging from 0.38 to 8.5 µg/mL for various stages of viral infection​ ​. However, Cladophora spp. polysaccharides exhibit a unique combination of low toxicity and effective antiviral properties, making them promising candidates for further development.

Mechanism of Action

The antiviral mechanism of algal polysaccharides is primarily attributed to their ability to interfere with viral adsorption and entry into host cells. The sulfated polysaccharides can bind to viral glycoproteins, preventing them from interacting with host cell receptors. This inhibition disrupts the viral life cycle at an early stage, reducing the overall viral load and preventing the spread of infection.

Recent Advances and Future Directions

Recent advances in gene editing and vaccine development have also shown promise in the fight against HSV. For instance, a study published in Nature Communications reported significant progress in gene therapy for HSV-1, showing a reduction in viral load and shedding through a simplified gene editing treatment​​. Additionally, a new trivalent herpes vaccine has demonstrated nearly 100% efficacy in early animal testing, offering hope for future human trials​.

These advancements, coupled with the ongoing research into natural antiviral agents like algal polysaccharides, highlight the potential for developing more effective and safer treatments for HSV infections.

Conclusion

The exploration of algal polysaccharides, particularly from Cladophora spp., presents a promising avenue for HSV treatment. These natural compounds offer a potential alternative to conventional antiviral drugs, with the added benefits of low toxicity and broad-spectrum antiviral activity. As research continues to advance, the integration of natural substances with innovative therapeutic approaches, such as gene editing and vaccine development, could pave the way for more effective and sustainable solutions to combat HSV infections.

This comprehensive review underscores the importance of continued research and collaboration in the development of new antiviral therapies. The fight against HSV is far from over, but the progress made thus far provides a solid foundation for future breakthroughs in the treatment and prevention of herpes simplex virus infections.


reference link : https://link.springer.com/article/10.1038/s41598-024-60941-7

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