Silver nanoparticles produced by the fungus Trichoderma reesei could become important allies in the prevention and treatment of COVID-19. Tests carried out on hamsters showed that they not only inhibited the infection but also reduced the viral load in the lungs, easing inflammation in the rodents.
The study, supported by FAPESP , paves the way for the development of nasal sprays and other products to combat several viral diseases, such as HIV/AIDS, shingles and influenza.
Silver nanoparticles have been of interest to the pharmaceutical industry due to their high affinity for proteins. Depending on their shape and size, they attract and adhere to these molecules, inhibiting the progression of disease.
"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%," says Roberto do Nascimento Silva , professor in the Department of Biochemistry and Immunology at the Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP) in Brazil and author of the study published in the journal Current Research in Biotechnology.
Tests in hamsters have shown that the effects of the product may go beyond preventing COVID-19. "The most interesting thing is that the nanoparticles not only prevented the virus from entering the cells but were also able to improve acute lung inflammation, one of the worst complications of COVID-19, proving to be a viable treatment for the disease," he says.
The researchers found that the silver nanoparticles prevented the activation of the inflammasome – a protein complex in cells responsible for the excessive immune response (cytokine storm) in severe COVID-19 – and the production of interleukin-1beta (IL-1β), a protein involved in the inflammatory response.
"We still need to deepen our understanding of which mechanism is involved in inhibiting the inflammatory response, but given the highly inflammatory nature of COVID-19, it can be inferred that silver nanoparticles reduce this process of cell damage that's usually associated with disease exacerbation and fatalities," says Silva.
The work was carried out in collaboration with researchers from FMRP-USP, the Oswaldo Cruz Foundation (Fiocruz, affiliated with the Ministry of Health), the Federal University of Alagoas (UFAL) and the University of Brasília (UnB). The group obtained the silver nanoparticles from T. reesei, known for its industrial application in the conversion of cellulose – an important component of plant biomass – into glucose.
In the laboratory, the fungus begins to multiply in a low-oxygen environment, producing a series of reducing enzymes like a biofactory. These molecules transform the silver into spherical nanoparticles. It is worth noting that the enzymes and proteins present in the T. reesei culture medium act as reducing and stabilizing agents, facilitating the formation of silver nanoparticles with controllable sizes and shapes.
"The biological production of silver nanoparticles is a sustainable biotechnological solution because it avoids the use of toxic chemicals. These nanoparticles can be used in nasal spray formulations, disinfectants, antimicrobial coatings and in medical devices to prevent the spread of the virus," he says.
Silva also points out that the study, conducted with the aim of stopping the spread of SARS-CoV-2, could serve as a basis for treating other viral diseases. "This strategy has proven to be very interesting, generating products for agriculture and the medical and pharmaceutical industries. 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," he says.
Although silver is expensive, says the researcher, the production of nanoparticles can be scaled up to produce low-cost products. Another important issue is dosage. "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," he says. "The next step in this work is to patent a pharmaceutical formulation and start clinical trials."
About FAPESP
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the state of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration.
