Short Human Peptide Shows Promise Against Deadly Fungal Eye Infections

Researchers from Hyderabad-based LV Prasad Eye Institute (LVPEI) in collaboration with the Bose Institute, Kolkata, an autonomous institute under the Department of Science and Technology, and other national and international partners, have identified a small human-derived peptide that could offer a safer and more effective alternative to existing antifungal drugs for treatment of sight-threatening fungal Keratitis.

A severe infection of the cornea, fungal Keratitis remains a major but often overlooked public health problem, particularly in India. Often described as a “slow epidemic”, corneal fungal infections disproportionately affect people engaged in agriculture, where minor eye injuries caused by plant material can allow fungi to enter the eye.

In urban settings, poor contact-lens hygiene and overuse of lenses are emerging risk factors. In many advanced cases, corneal transplantation becomes the only option to save vision.

Now, the new discovery by the researchers from the LV Prasad Eye Institute and Bose Institute offers a ray of hope. They have shown that a tiny 15-amino-acid fragment, known as SA-XV, can effectively kill disease-causing fungi while also supporting healing of damaged corneal cells.

The research builds on earlier work on S100A12, a natural antimicrobial protein produced by the human immune system. While S100A12 is known to have antifungal properties, its large size makes it expensive to manufacture and difficult to deliver into the eye. To overcome these challenges, the team searched for a shorter fragment that could retain the parent protein’s antifungal strength.

They found that the final 15 amino acids of S100A12 — SA-XV — were sufficient to stop fungal growth. Laboratory tests showed that SA-XV reduced the growth of both Fusarium and Candida by more than 99%. Crucially, it achieved this without damaging human corneal cells, a key requirement for any eye medication.

Further experiments revealed how the peptide works. SA-XV first binds to the fungal cell wall and membrane, then penetrates the cell. Inside, it disrupts multiple vital processes — damaging the mitochondria, interfering with DNA function, triggering oxidative stress, and ultimately causing fungal cell death. This multi-step attack makes it harder for fungi to develop resistance, a growing problem with current antifungal drugs.

The peptide’s effectiveness was also tested in a mouse model of fungal keratitis. When applied directly to the eye, SA-XV significantly reduced fungal load and promoted healing of the corneal surface. This dual benefit — fighting infection while aiding tissue repair — is particularly valuable in eye infections, where preserving vision is paramount.

The researchers also found that shortening the peptide any further caused it to lose its antifungal effect, underlining the importance of its precise structure. Unlike many broad-spectrum antifungals, SA-XV appears to act selectively, targeting specific fungi while sparing others.

Experts say the findings are especially significant for India, where existing antifungal medicines often have serious limitations. Many drugs are toxic, have poor penetration into the eye, or are becoming less effective due to rising resistance. These challenges are particularly dangerous for people with weakened immune systems, in whom fungal infections can quickly turn fatal.

In the study published in the,” Journal of Biological Chemistry”, Dr. Sanhita Roy and her team from L V Prasad Eye Institute, and Professor Anirban Bhunia and his team from Bose Institute along with other collaborators said hat these antimicrobial peptides are non-toxic, serum-stable, and effective in inhibiting the growth of both planktonic and biofilm forms of Fusarium and Candida species.

The other researchers in the team included Riddhi Agarwal, Karishma Biswas, Akshita Agrawal, Srijita Kundu and Dipanwita Roy, with some of the team members also affiliated with the Graduate Studies programme at the Manipal Academy of Higher Education, Manipal.

Researchers Nisha Nandhini Shankar and Ragothaman M Yennamalli are from the School of Chemical and Biotechnology at SASTRA Deemed to be University, Thanjavur, international collaborators included DeokHyun Son and DongKuk Lee from the Department of Fine Chemistry at Seoul National University of Science and Technology, with Son also affiliated with SP2Therapeutics Inc. in Seoul, and Amaravadhi Harikishore from the School of Biological Sciences at Nanyang Technological University, Singapore.

While further studies are needed before SA-XV can be tested in humans, researchers say the discovery opens the door to developing affordable, human-derived antifungal treatments. Such therapies could play a crucial role in preventing blindness from fungal eye infections, particularly in low- and middle-income countries where the disease burden remains high.

In India, Fusarium and Candida species account for most cases of fungal keratitis. The World Health Organization (WHO) has now recognised these infections as a priority public health concern.