Brazilian researchers discover two novel peptides with biotechnological potential in snake venom
Fragments of hemorrhagic toxins that may help treat high blood pressure were found in the venom of the pit viper Cotiara, which inhabits the South of Brazil, and that of the South American bushmaster, a denizen of tropical rainforests
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THE VENOM OF THE SOUTH AMERICAN BUSHMASTER (LACHESIS MUTA) IS NOT ESPECIALLY POWERFUL, BUT THE SNAKE IS DANGEROUS BECAUSE OF THE LARGE AMOUNT OF VENOM IT INJECTS INTO ITS VICTIMS
view moreCREDIT: SÁVIO STEFANINI SANT’ ANNA/INSTITUTO BUTANTAN
Brazilian snake and spider venoms continue to be a source of new discoveries with biotechnological potential. Two studies supported by FAPESP and recently published show how this is possible even in relatively well-studied species such as the lancehead pit viper Cotiara (Bothrops cotiara) and the South American bushmaster (Lachesis muta).
“Venoms never cease to surprise us. Even with so much accumulated knowledge, fresh discoveries are possible, such as unpredictable fragments that are parts of known proteins. Despite all the available technology, a great deal remains to be studied in these toxins,” said Alexandre Tashima, principal investigator for both studies. Tashima is a professor at the Federal University of São Paulo’s Medical School (EPM-UNIFESP) and is supported by FAPESP.
He was referring to a novel peptide (protein fragment) identified in B. cotiara’s venom and named Bc-7a. Although it is part of a protein that causes bleeding in the snake’s prey, in functional terms it is closer to peptides such as those at the origin of captopril, a drug that lowers blood pressure by inhibiting the activity of angiotensin-converting enzyme (ACE).
The latest study is reported in an article published in the journal Biochimie.
Many ACE-inhibiting molecules already exist, but the search continues because of adverse side effects such as a dry cough, dizziness, and high blood potassium levels.
The peptide is one of 197 revealed by the study, 189 of them reported for the first time. In 2012, the group found 73 peptides in the same snake’s venom. According to the authors, the difference is due to the use in the more recent study of faster and more sensitive equipment than was available a decade ago, and to the larger number of peptide sequences to be gleaned from databases now.
In previous studies, Tashima and his group had found molecules with biotechnological potential in the venom of another snake, as well as two tarantula spiders (read more at: agencia.fapesp.br/35106 and agencia.fapesp.br/40490).
Bushmaster
A study involving bushmaster venom from L. muta, reported in an article published in Biochemical and Biophysical Research Communications, identified 151 peptides, of which 126 were previously unknown.
The researchers were particularly interested in a novel metalloproteinase-derived peptide called Lm-10a, a fragment of a hemorrhagic toxin that inhibits ACE and could potentially be used in a drug to treat blood pressure. Their analysis suggested that both Lm-10a from L. muta and Bc-7a from B. cotiara resulted from fragmentation processes during venom maturation in the snake’s venom gland and that many more novel peptides could be obtained from the toxins.
“In this kind of analysis, the protein sequence obtained is just a snapshot. Cleavage, enzymatic degradation and other processes generating novel peptides that aren’t necessarily detected occur all the time,” Tashima explained.
More research is needed to verify the real potential of the peptides they discovered. Moreover, the dynamic nature of toxin maturation points to the use by venomous snakes of various biological mechanisms to refine venom during their evolution.
“Despite advances in sequencing technology and the production of large amounts of data in recent years, much remains to be discovered about the vast universe of peptides and their biological roles. We must take advantage of our good fortune in being able to study these species, many of which will be extinct before they’ve even been discovered,” Tashima said.
About São Paulo Research Foundation (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. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.
JOURNAL
Biochimie
ARTICLE TITLE
A novel metalloproteinase-derived cryptide from Bothrops cotiara venom inhibits angiotensin-converting enzyme activity
Incomplete notification and underreporting of snakebites can hinder public health actions, study suggests
Better data will help improve research and antivenom distribution. A survey conducted in a Brazilian state with the country’s second-highest number of ophidic accidents draws attention to the need to train health workers to complete notification forms
Peer-Reviewed PublicationApproximately 28,000 snakebites caused by venomous snakes of medical importance are reported annually in Brazil, according to Health Ministry data. The number is certainly a significant underestimate because many snakebites are not reported.
Underreporting of ophidic accidents (the technical term for poisoning by snakebite), especially in rural areas, is a structural problem in Brazil and other countries. As part of an effort to tackle the problem, notification of snakebites has been mandatory for health clinics and hospitals in Brazil since 1986, and the resulting statistics are key inputs to public health policy actions, such as production and distribution of antivenoms.
However, a study reported in Revista da Sociedade Brasileira de Medicinal Tropical shows that the requisite forms are not always properly completed and often contain information that is probably incorrect, given the mismatch between the symptoms mentioned and the species named as the cause of the accident.
The authors of the article retrospectively analyzed the clinical and epidemiological profiles of snakebites in Maranhão state, Northeast Brazil, between January 2009 and December 2019. According to the study, 17,658 snakebites by venomous snakes of medical importance were reported in Maranhão in the period.
The authors point to a “lack of systematic government planning and adequate training for health professionals to complete compulsory notification forms correctly … at the national and state levels”.
“Health workers aren’t trained to complete the forms properly, and this hinders the planning of public health policy to address ophidic accidents. Insufficient knowledge of the most common species and symptoms involved is another problem,” said Sâmia Caroline Melo Araújo, first author of the article. The study was conducted as part of her master’s research at the State University of Maranhão (UEMA).
The authors advocate short-term actions to train health workers to recognize ophidic accidents involving clinically important snake species, provide better care for patients, and complete notification forms correctly. Research in the field will be able to advance as a result.
“The latest data on this topic in Brazil and worldwide is from at least five years ago. The main problem is incompleteness, as snakebites are underreported, not least in Maranhão, which ranks second among Brazilian states in official numbers of ophidic accidents,” Thaís Guedes, corresponding author of the article, told Agência FAPESP.
Guedes is a professor at the State University of Campinas’s Institute of Biology (IB-UNICAMP), and principal investigator for the project “Evolution and biogeography of the herpetofauna: patterns, process and implications for conservation in a scenario of environmental and climate changes”, which is supported by FAPESP. One of its aims is to identify areas of Brazil where the risk of ophidic accidents is significant (read more at: agencia.fapesp.br/40692).
Statistics
The analysis showed that 66% of snakebite victims lived in rural areas of Maranhão, where 82% of snakebite accidents occurred. No information on the victims’ home addresses or accident locations was included in 2%-3% of the reports. Rural laborer was the occupation stated for 45% of the victims; no information on the victim’s occupation was reported in 31% of the cases. Men accounted for 77% of the victims.
The snakes that caused the most accidents were species of the genus Bothrops (lanceheads, 67%), followed by Crotalus (rattlesnakes, 24%).
Micrurus (coral snakes) and Lachesis (bushmasters) each caused 1% of cases.
Feet were bitten in 53% of cases, legs in 21%, and hands in 10%. About 58% of the victims received medical care within three hours, which is roughly the time limit to avoid severe complications and death.
Just over half the cases were classified as mild, and 81% of the victims recovered, but 139 deaths (1%) were recorded.
The researchers found that severity of envenomation correlated significantly with age, snake genus, and time until the start of medical care. Victims aged 51-60 years were most likely to have severe symptoms, followed by over-60s.
Underreporting of snakebites is a global problem, as already noted. According to the World Health Organization (WHO), the number of snakebite victims worldwide is between 4.5 million and 5.4 million per year, with 1.8 million-2.7 million developing clinical illness, and 81,000-138,000 dying from complications. High-risk groups include agricultural workers, herders, fishermen, hunters, working children, and people living in poorly constructed houses.
In the Brazilian study, 45% of the victims stated their occupation to be agricultural workers, followed by school students, with 16%. “A large proportion of the snakebite accidents reported in the period in Maranhão occurred during January and March, when agricultural activity peaks, with a higher probability of encounters between humans and snakes. If all rural workers wore boots, gaiters and gloves, the number of medically important snakebites would drop by as much as 90%, we believe. Proper healthcare and notification could reduce the number of fatal victims and those with complications,” Guedes said.
About São Paulo Research Foundation (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. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.
ARTICLE TITLE
Snakebites in Northeastern Brazil: accessing clinical-epidemiological profile as a strategy to deal with Neglected Tropical Diseases
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