Caterpillar protein acts against measles and H1N1

Antiviral substance found in insects of the Megalopygidae family (such as Megalopyge lanata) also acts against picornavirus, which belongs to the family of viruses that cause poliomyelitis.

By Thereza Venturoli

Agência FAPESP – More than half of all known species of animals are insects. But how have species with immune systems that are so poorly developed – particularly when compared to those of mammals – evolved over 350 million years and survived in the most varied and even the most hostile environments on the plant?

Studies indicate that the secret lies in the substances found in hemolymph, the fluid that functions as blood in insects. It is these substances that have the capacity to combat viruses, bacteria and fungi in these animals. These substances also have the potential to reduce the action of viruses in humans, and understanding these substances and their mechanism of action is major step toward the development of new medicines.

Researchers from the Butantan Institute in São Paulo have discovered promising substances in caterpillars. “Antiviral substances have long been searched for in some animal and plant products, such as sea urchins and propolis, whereas little investigation has occurred in insects and even less in caterpillars,” commented Ronaldo Zucatelli Mendonça, the virologist responsible for the study “Bioprospection of proteins of pharmacological and biotechnological interest in hemolymph from caterpillars in the Megalopygidae family,” which was funded by FAPESP.

Mendonça’s strategy was to investigate highly potent antiviral substances in caterpillars of the Megalopygidae family. “We still do not know the exact chemical composition of this substance,” he said. “However, an unequivocal action has already demonstrated: it reduced the replication of picornavirus (the virus causing poliomyelitis) by 2,000 times, lowered measles virus replication by 750 times and neutralized the H1N1 flu virus.”

Furthermore, according to the study coordinator, this data is preliminary. “By the conclusion of the study, we could reach an even greater reduction,” he said.

The study with Megalopygidae is the continuation of a previous project during which the team isolated and purified a protein from a caterpillar in the Saturniidae family, Lonomia obliqua.

The protein found in Lonomia diminished the replication of the herpes virus by 1 million times and the replication of the rubella virus by 10,000-fold. The study was published in Antiviral Research in 2012.

The two studies on Lonomia and Megalopygidae family caterpillars focused on substances that present two specific properties: apoptotic and antiviral actions. The first promotes apoptosis (programmed cell death that is triggered to quickly eliminate unnecessary and damaged cells), an important process in the control mechanism for cancer. The current focus of the study with the Megalopygidae caterpillar is with regard to its antiviral action.

The proteins under study are produced by recombinant DNA technology. The gene encoding the protein is extracted from the hemolymph and cloned into a baculovirus (a virus that infects insect cells). It is then replicated in the insect cells, producing defense proteins (recombinant proteins) in large quantities.

“The main advantage of producing a recombinant protein is that this makes the extraction of the substance simpler and on a larger scale,” comments Mendonça. “Before it can be industrialized, however, we must verify its action in organisms using in vivo testing and evaluate its economic feasibility.”

The caterpillars studied by Mendonça’s team are among the stinging caterpillars that are harmful to humans. Their bristles release a venom that can cause death. The two species were chosen for further research due to the accumulation of hundreds of carcasses of these insects at the Butantan Institute, which are left over after their venom is extracted to produce anti-burn sera. It is from these carcasses that scientists obtained the hemolymph from which the genes of the defense substances can be extracted.

The Megalopygidae family encompasses more than 200 species, including Megalopyge lanata and Megalopyge albicollis.

According to Mendonça, the studies with Lonomia and Megalopygidae family caterpillars constitute a gateway to further highly relevant research. “Brazil has a megabiodiversity in insects, and all of them could have substances of this type with much greater action than those discovered to date,” said the researcher, who completed three post-doctoral projects with FAPESP fellowships in Portugal and Mexico.