A team of Brazilian researchers, led by Roberto do Nascimento Silva, PhD, a professor at Ribeirão Preto Medical School, University of São Paulo, has shown that silver nanoparticles synthesized by the fungus Trichoderma reesei have been shown to inhibit SARS-CoV-2 infection and reduce lung inflammation in animal models. This finding, published in Current Research in Biotechnology, provides a potential pathway to developing antiviral treatments such as a nasal spray to treat COVID-19 and potentially other viral diseases.
“Using computer analysis, we found that the silver nanoparticles produced in our laboratory bind to the spike protein, a kind of key that the SARS-CoV-2 virus uses to enter the host cells and replicate. In this way, they inhibit the entry of the virus into the cell by 50%,” said Silva, the study’s senior author.
The team behind the research included scientists from the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP), the Oswaldo Cruz Foundation (Fiocruz), the Federal University of Alagoas, and the University of Brasília. Their experiments demonstrated that the biologically produced silver nanoparticles (AgNPs) significantly reduced viral replication in the lungs of Syrian hamsters. In addition to inhibiting infection, the AgNPs also prevented the activation of inflammasomes and production of IL-1β, a protein associated with intensified immune reaction seen in some of the most severe cases of COVID-19.
To synthesize the silver nanoparticles, the investigators used a low-oxygen environment using T. reesei, a fungus that is commonly used to break down plant biomass. The fungus was cultivated in conditions that promoted the secretion of reducing enzymes that supported the conversion of silver ions to silver nanoparticles.
These enzymes also stabilized the nanoparticle structure, allowing the team to control the size and shape of the nanoparticles, which influences how nanoparticles interact with viruses and host cells. Their process could prove to be a viable pathway to developing effective treatments.
“The biological production of silver nanoparticles is a sustainable biotechnological solution because it avoids the use of toxic chemicals,” Silva said. “These nanoparticles can be used in nasal spray formulations, disinfectants, antimicrobial coatings, and in medical devices to prevent the spread of the virus.”
The new research builds on earlier efforts to understand the antiviral properties of silver nanoparticles, which have shown in animal studies that they can be effective against a range of viruses, including HIV and herpes simplex virus.
In vivo studies in hamsters conducted by the researchers further support the antiviral and anti-inflammatory effects of these nanoparticles.
“AgNPs treatment significantly alleviated acute lung injury induced by SARS-CoV-2 infection in Syrian hamsters. This suggests that AgNPs treatment effectively impairs viral replication or propagation within lung tissue, highlighting its potential as an antiviral agent against SARS-CoV-2,” the researchers wrote.
Unlike traditional chemical methods of nanoparticle synthesis, which can be costly and harm the environment, fungi-assisted green synthesis is seen as more scalable and sustainable. The fungus’s natural ability to reduce and stabilize metal ions enables large-scale production with minimal toxicity.
That noted, the team is cognizant of the toxicity of silver to humans and worked to find a way to use it with minimal harm.
“Silver is toxic. That’s why we use a very low dosage, ten times less than what’s considered toxic to the body. And after eight weeks, the body is able to eliminate the metal from the body. So the cost-benefit is worth it,” said Silva.
The potential for using this method for treatment extends beyond COVID-1,9 and similar approaches could be developed for other viral diseases, including HIV/AIDS, shingles, and influenza.
“This strategy has proven to be very interesting, generating products for agriculture and the medical and pharmaceutical industries,” Silva said. “Originally, my laboratory investigated the use of silver nanoparticles to fight breast tumor cells. With the pandemic, we focused our work on fighting SARS-CoV-2. The application is broad, and there’s already work in animal studies for HIV and the herpes virus, for example.”
While this research is still in the preclinical stage, the findings have implications for clinical care. If developed into pharmaceuticals, silver nanoparticles could provide an alternative or complementary therapy to current antiviral drugs, particularly in managing inflammation. Further investigation will be needed to determine the nanoparticles’ mechanisms of action, optimal dosages, long-term safety, and potential side effects.
