ዘመቻው በእውቀት የታገዘ ቢሆን

የኮሮና ቫይረስ በለጸጉ በተባሉ የአውሮፓና ሰሜን አሜሪካ አገራት እያደረሰ ያለውን ቀውስ በሚገባ ለተገነዘበ፣በሽታው እንደ ኢትዮጵያ ባሉ  ታዳጊ አገራት  ሊያስከትለው የሚችለውን መጠነ ሰፊ ውድመት መገመት አያዳግትም።  ለዚህም ነው የበሽታውን ስርጭት ለመግታት ብቸኛ አማራጭ የሆነውን መከላከልን ከበለጸጉ አገራት በላቀ መልኩ ልንተገብር ግድ የሚለን። ምክንያቱም ቫይረሱ በሰፋት ከተሰራጨ በኋላ ለመቆጣጠር አቅሙ የለንም።  በሃገራችን የኮሮና ቫይረስን ስርጭት ለመግታት የሚደረገው ዘመቻ የተሳካ ሊህን የሚችለው  በእውቀትና መረጃ ላይ የተመሰረተ ሲሆን ብቻ ነው። ከዙህም አንጻር  ቫይረሱ ሊስፋፋ የሚችልባቸውንና መከላከያ መንገዶችን ለሀዝቡ ማስረዳት ቀዳሚው ርምጃ ሊሆን ይገባዋል፡፡ በሽታውን አስመልክቶ ሳይንሳዊ ትንታኔወችንና የመስጠና መመሪያውችን የማውጣት ሚና የጤና ባለሙያዎች መሆኑ እንደተጠበቀ ሆኖ  መረጃው በመተንተን ህብረተሰቡን የማሳወቅና የማስጠንቀቅ ሃላፊነት ደግሞ የመገናኛ ብዙሃን ድርሻ ነው፡፡ ይሁን እንጂ አሁን እየተስተዋሉ ያሉ ኮሮናን የተመለክቱ ዘገባዎች መገናኛ በዙሃን በተገቢው መልኩ ሚናችውን እየተወጡ ነው ብሎ ለመደምደም የሚያስችሉ አይደሉም፡፡

ይህን እንድል ያስገደደኝ በሽታው በኢትዮጵያ መከስቱን ተከትሎ በተለያዩ መገናኛ ብዙሃንና በማህብራዊ ድረግጾች የሚደረጉ ዘገባውች የመረጃ እጥረት ያለባቸውና በበቂ ግንዛቤ ያልታገዙ ልስለመሰለኝ ነው፡፡ይልቁንም ግልብነትና ጥራዝነጠቅነት ይስተዋልባችዋል፡፡

የኮሮና ቫይረስ አዲስ ከመሆኑ ጋር ተያይዞ  በሽታውን የተመለከቱ መረጃውች  የተውረሱና  ከእንግሊዝኛው ቋንቋ ተተረጎሙ ሊሆኑ እንደሚችሉ ግልጽ ነው፡፡ዪሁን እንጂ ትርጉም በብቅና በትክክል መልክትን ማስተላልፍ ካልቻለ ክጥቅሙ ይልቅ ጉዳቱ ያመዝናል፡፡በተለይም እንደዚህ አይንት ወረርሽኝ በሚከስትባት ወቅት የመገናኛ ብዙሃን መረጃ የመስጠትና የማስተማር ሃላፊነት ከፍተኛ ነው።

የመናኛ ብዙሃን አንዱና ዋነኛው ችግር ቃላትንና ጽንሰ ሃሳቦችን በተገቢውና ትርጉም በሚስጥ መልክ መተርጎም አለምቻል ነው፡፡

ለአብነት ያህል  social distancing የሚለውን ጽንስ ሃሳብ ብቻ ብንመለከት የመገናኛ ብዙሃን ሊተረጉሙ የሞከሩበት መንግድ ወጥነትና ግልጽነት የጎደለው ነው፡፡ ብዙዎች ማህበራዊ ርቅት የሚል ትርጋሜ ስጥተውታል፡፡ማህበራዊ ረቅት  በቅጥታ የተተረጎመ ቢሆንም የተፈለገውን ትርጉም ግን በአግባቡ የሚያስተላልፍ አይደለም፡፡

የጋዜጠኝንት ሙያ ከሚመራባቸው  መሰረታዊ መርሆች አንደኛው መልክትን በቀላሉና ተራው ህበረሰብ ሊረዳው በሚችለው ቋንቋ ማቅረብ መቻል ነው፡ ከዚህ አንጻር social distancing የሚለውን ጽንሰ ሃሳብ ቀለል ባለ ቋንቋ ለህብረተሰቡ ማስረዳት ይቻላል፡፡ ከ“ማህብበራዊ ርቀት” ይልቅ የገጽ ለገጽ ቅርርብና ንክኪን ማስወገድ/ ከለሎች ሰወች ጋር መቀራረብን ማስቅረት ይህን ማድረግ ካልተቻለ ለአደጋ የማያጋልጥ ርቀትን መጠበቅ/ ማህበራዊ ግንኙነትን መሰረዝ፤…ወዘተ በሚል መተካት ይቻላል።

 

Scientists figure out how new coronavirus breaks into human cells

By Stephanie Pappas – Live Science Contributor

Scientists have revealed the first picture of how the new coronavirus SARS-CoV-2 binds with human respiratory cells in order to hijack them to produce more viruses.

Researchers led by Qiang Zhou, a research fellow at Westlake University in Hangzhou, China, have revealed how the new virus attaches to a receptor on respiratory cells called angiotensin-converting enzyme 2, or ACE2.

“They have pictures all the way down at the level of the atoms that interact at the binding interface,” Thomas Gallagher, a virologist at Loyola University Chicago who was not involved in the new research but studies coronavirus structure, told Live Science. That level of information is unusual at this stage of a new virus outbreak, he said.

“The virus outbreak only began to occur a couple months ago, and within that short period of time, these authors have come up with information that I think traditionally takes much longer,” Gallagher said.

That’s important, he said, because understanding how the virus enters cells can contribute to research on drugs or even a vaccine for the virus.

A viral entryway

To infect a human host, viruses must be able to gain entry into individual human cells. They use these cells’ machinery to produce copies of themselves, which then spill out and spread to new cells.

On Feb. 19 in the journal Science, a research team led by scientists at the University of Texas at Austin described the tiny molecular key on SARS-CoV-2 that gives the virus entry into the cell. This key is called a spike protein, or S-protein. Last week, Zhou and his team described the rest of the puzzle: the structure of the ACE2 receptor protein (which is on the surfaces of respiratory cells) and how it and the spike protein interact. The researchers published their findings in the journal Science on March 4.

“If we think of the human body as a house and 2019-nCoV [another name for SARS-CoV-2] as a robber, then ACE2 would be the doorknob of the house’s door. Once the S-protein grabs it, the virus can enter the house,” Liang Tao, a researcher at Westlake University who was not involved in the new study, said in a statement.

Zhou and his team used a tool called cryo electron microscopy, which employs deeply frozen samples and electron beams to image the tiniest structures of biological molecules. The researchers found that the molecular bond between SARS-CoV-2’s spike protein and ACE2 looks fairly similar to the binding pattern of the coronavirus that caused the outbreak of SARS in 2003. There are some differences, however, in the precise amino acids used to bind SARS-CoV-2 to that ACE2 receptor compared with the virus that causes SARS (severe acute respiratory syndrome), the researchers said.

“While some might consider the differences subtle,” Gallagher said, “they might be meaningful with respect to the strength with which each of those viruses stick.”

That “stickiness” could affect how easily a virus transmits from one person to another. If any given viral particle is more likely to enter a cell once it enters the human body, transmission of disease is more likely.

There are other coronaviruses that circulate regularly, causing upper respiratory infections that most people think of as the common cold. Those coronaviruses don’t interact with the ACE2 receptor, Gallagher said, but rather, they get into the body using other receptors on human cells.

Coronavirus structure implications

The structure of SARS-CoV-2’s “key” and the body’s “lock” could theoretically provide a target for antiviral drugs that would stop the new coronavirus from getting into new cells. Most antiviral drugs already on the market focus on halting viral replication within the cell, so a drug that targeted viral entry would be new territory, Gallagher said.

“There is no effective clinical drug that will block that interaction that I know of” that’s already in use, he said.

The viral spike protein is also a promising target for vaccines, because it’s the part of the virus that interacts with its environment and so could be easily recognized by the immune system, Gallagher said.

Even so, developing either drugs or a vaccine will be a challenging task. Treatments and vaccines not only have to prove effective against the virus, but must also be safe for people, Gallagher said. U.S. Centers for Disease Control and Prevention officials have said that the earliest a coronavirus vaccine could be available is in a year to a year and a half. ( Source: Live Science)

COVID-19 coronavirus epidemic has a natural origin

The novel SARS-CoV-2 coronavirus that emerged in the city of Wuhan, China, last year and has since caused a large scale COVID-19 epidemic and spread to more than 70 other countries is the product of natural evolution, according to findings published today in the journal Nature Medicine.

The analysis of public genome sequence data from SARS-CoV-2 and related viruses found no evidence that the virus was made in a laboratory or otherwise engineered.

“By comparing the available genome sequence data for known coronavirus strains, we can firmly determine that SARS-CoV-2 originated through natural processes,” said Kristian Andersen, PhD, an associate professor of immunology and microbiology at Scripps Research and corresponding author on the paper.

In addition to Andersen, authors on the paper, “The proximal origin of SARS-CoV-2,” include Robert F. Garry, of Tulane University; Edward Holmes, of the University of Sydney; Andrew Rambaut, of University of Edinburgh; W. Ian Lipkin, of Columbia University.

Coronaviruses are a large family of viruses that can cause illnesses ranging widely in severity. The first known severe illness caused by a coronavirus emerged with the 2003 Severe Acute Respiratory Syndrome (SARS) epidemic in China. A second outbreak of severe illness began in 2012 in Saudi Arabia with the Middle East Respiratory Syndrome (MERS).

On December 31 of last year, Chinese authorities alerted the World Health Organization of an outbreak of a novel strain of coronavirus causing severe illness, which was subsequently named SARS-CoV-2. As of February 20, 2020, nearly 167,500 COVID-19 cases have been documented, although many more mild cases have likely gone undiagnosed. The virus has killed over 6,600 people.

Shortly after the epidemic began, Chinese scientists sequenced the genome of SARS-CoV-2 and made the data available to researchers worldwide. The resulting genomic sequence data has shown that Chinese authorities rapidly detected the epidemic and that the number of COVID-19 cases have been increasing because of human to human transmission after a single introduction into the human population. Andersen and collaborators at several other research institutions used this sequencing data to explore the origins and evolution of SARS-CoV-2 by focusing in on several tell-tale features of the virus.

The scientists analyzed the genetic template for spike proteins, armatures on the outside of the virus that it uses to grab and penetrate the outer walls of human and animal cells. More specifically, they focused on two important features of the spike protein: the receptor-binding domain (RBD), a kind of grappling hook that grips onto host cells, and the cleavage site, a molecular can opener that allows the virus to crack open and enter host cells.

Evidence for natural evolution

The scientists found that the RBD portion of the SARS-CoV-2 spike proteins had evolved to effectively target a molecular feature on the outside of human cells called ACE2, a receptor involved in regulating blood pressure. The SARS-CoV-2 spike protein was so effective at binding the human cells, in fact, that the scientists concluded it was the result of natural selection and not the product of genetic engineering.

This evidence for natural evolution was supported by data on SARS-CoV-2’s backbone — its overall molecular structure. If someone were seeking to engineer a new coronavirus as a pathogen, they would have constructed it from the backbone of a virus known to cause illness. But the scientists found that the SARS-CoV-2 backbone differed substantially from those of already known coronaviruses and mostly resembled related viruses found in bats and pangolins.

“These two features of the virus, the mutations in the RBD portion of the spike protein and its distinct backbone, rules out laboratory manipulation as a potential origin for SARS-CoV-2” said Andersen.

Josie Golding, PhD, epidemics lead at UK-based Wellcome Trust, said the findings by Andersen and his colleagues are “crucially important to bring an evidence-based view to the rumors that have been circulating about the origins of the virus (SARS-CoV-2) causing COVID-19.”

“They conclude that the virus is the product of natural evolution,” Goulding adds, “ending any speculation about deliberate genetic engineering.”

Possible origins of the virus

Based on their genomic sequencing analysis, Andersen and his collaborators concluded that the most likely origins for SARS-CoV-2 followed one of two possible scenarios.

In one scenario, the virus evolved to its current pathogenic state through natural selection in a non-human host and then jumped to humans. This is how previous coronavirus outbreaks have emerged, with humans contracting the virus after direct exposure to civets (SARS) and camels (MERS). The researchers proposed bats as the most likely reservoir for SARS-CoV-2 as it is very similar to a bat coronavirus. There are no documented cases of direct bat-human transmission, however, suggesting that an intermediate host was likely involved between bats and humans.

In this scenario, both of the distinctive features of SARS-CoV-2’s spike protein — the RBD portion that binds to cells and the cleavage site that opens the virus up — would have evolved to their current state prior to entering humans. In this case, the current epidemic would probably have emerged rapidly as soon as humans were infected, as the virus would have already evolved the features that make it pathogenic and able to spread between people.

In the other proposed scenario, a non-pathogenic version of the virus jumped from an animal host into humans and then evolved to its current pathogenic state within the human population. For instance, some coronaviruses from pangolins, armadillo-like mammals found in Asia and Africa, have an RBD structure very similar to that of SARS-CoV-2. A coronavirus from a pangolin could possibly have been transmitted to a human, either directly or through an intermediary host such as civets or ferrets.

Then the other distinct spike protein characteristic of SARS-CoV-2, the cleavage site, could have evolved within a human host, possibly via limited undetected circulation in the human population prior to the beginning of the epidemic. The researchers found that the SARS-CoV-2 cleavage site, appears similar to the cleavage sites of strains of bird flu that has been shown to transmit easily between people. SARS-CoV-2 could have evolved such a virulent cleavage site in human cells and soon kicked off the current epidemic, as the coronavirus would possibly have become far more capable of spreading between people.

Study co-author Andrew Rambaut cautioned that it is difficult if not impossible to know at this point which of the scenarios is most likely. If the SARS-CoV-2 entered humans in its current pathogenic form from an animal source, it raises the probability of future outbreaks, as the illness-causing strain of the virus could still be circulating in the animal population and might once again jump into humans. The chances are lower of a non-pathogenic coronavirus entering the human population and then evolving properties similar to SARS-CoV-2.

Funding for the research was provided by the US National Institutes of Health, the Pew Charitable Trusts, the Wellcome Trust, the European Research Council, and an ARC Australian Laureate Fellowship ( Source: Science Daily).

 

Awareness Key to Contain Pandemic

By Aregu B. Wondimuneh
I found the news that a person suspected of contracting the corona virus was caught trying to escape a quarantine facility troubling. It goes without saying that this person fears the stigma attached to being quarantined or other related consequences more than the disease itself. This might be a single incident but is indicator of the grim reality of existing information gap and one that should make health authorities and the public at large worried. Stigma and lack of awareness have always played a negative role in the fight against any form of pandemic. People who are afraid of stigma or who try to avoid quarantine will without doubt complicate the efforts being deployed to control the pandemic and pose a heavy burden to the already struggling healthcare system. So, health officials should give as much attention to the creation of a thorough public understanding about the nature of Covid-19 and the controlling mechanisms.

Egypt is entangled in its old win-lose strategy

Aregu B. Wondimuneh
It has done it before, and it is doing it again. When the technical and legal experts and ministers of water and foreign affairs of Egypt, Sudan and Ethiopia concluded rounds of talks without a comprehensive document to settle the issues regarding the filling and operation of the Grand Ethiopian Renaissance Dam (GERD). it wasn’t entirely unexpected. Discussions of similar nature were held for several times in the past and the results were predictable. Egypt has always positioned itself as one who must get the better end of the deal.
In the pass, Egypt exhausted every means within its power to make sure its monopoly over River Nile was unchallenged and negotiations regarding utilization of the river water with the Ethiopia or other riparian countries, for that matter were off the table. Its leaders have in effect refused to recognize Ethiopia’s right to have a fair share of the Blue Nile River to which it is not only the source but also contributor of 87 of the water. Instead of working on a mutually beneficial and win-win approach, Egypt made it a strategy for decades to either threaten Ethiopia not to utilize the River water or ally themselves with the internal and external enemies of the country to make sure that it won’t be in any position to carry out any major projects on the River. In fact, that has been strategy all along until the launch of the Grand Renaissance Dam (GERD). Although the two countries have had long standing ties and share much more than just a river, their relationships have always been overshadowed by the water politics.
Ethiopia has for long remained hands tied and helplessly watched its largest river gushing out caring fertile soil washed away from the country’s highlands. If there existed any attempts on the Ethiopian part to build any form of development projects on the Blue Nile River, they were met with military threats from Egypt. Egyptian leaders also had no trouble convincing financial institutions to block any form of financial aid to Ethiopia.
As a result, Egypt had neither the interest nor the urge to work on any cooperation framework with Ethiopia. because Ethiopia was in no political or economic status that would allow it to carry out any major undertakings on the river water.
The launch of the Grand Renaissance Dam was not only an important milestone in the country’s effort to fil the huge power demand-supply gap. It also was a demonstration of the fact that the country is capable of undertaking projects of such nature with local resources. Egypt has been forced to come to the negotiation table because its old strategy will have no place any longer.
Egypt opposed the construction of the Dam from the very beginning. In fact, there were a couple of times the country’s newspapers reported that Egypt might use military force to stop the building of the dam. Now the Dam has reached its completion stage.
For many years now, Egypt has been enjoying its unchallenged monopoly over the utilization of River Nile. There was no agreement or treaty which Ethiopia is part of and that entitled Egypt to dictate who gets what when it comes to sharing the river water. The country relied on the its military might and geopolitical influence. However, Ethiopia, which is the source of the Blue Nile and contributor of 87 per cent of the water was literally ripped of all its rights to get the fair share of the river water, as a result of the direct and indirect influence of Egypt.
Egypt portrays itself as the creation of River Nile. Its leaders have always wanted the world to believe that any development projects on the river by the upper riparian countries will seriously jeopardize the country’s socioeconomic activities since the Nile is the only source of water for the country. True, the Nile is the major water source for Egypt’s economy. However, it is not the only waterbody available for the country. Egypt is surrounded by two other large water bodies, namely the Red Sea and the Mediterranean Sea. Like many of its neighbors in the Middle East and many other countries around the world Egypt has water resources that can be desalinated and utilized.
At times Egypt justifies its monopolistic right over the river with agreements that were concluded without even participating the source country. The so called agreements were concluded in 1929 and 1959 between Egypt and Sudan when both countries were British its colonies. Because Egyptian leaders relied much on the country’s military might and political influence for much of the country’s long history they seem to be struggling to face the reality that Ethiopia, as a source of the water and contributor of the larger share of the water has the right to utilize the water. That has been reflected on the recent negotiations.
According to experts, the GERD is less of a threat for the downstream countries including Egypt, In fact studies which were conducted on possible impact of the Dam even suggested that it has a positive contribution toward regulating the water flow and protecting flood occurrences particularly in the Sudan.
If there is one problem that is worrisome to not only to the downstream countries but also to upper stream countries including Ethiopia, it is climate change and deforestation which may seriously impact the water volume of the river. Egypt, Ethiopia as well the rest Nile riparian counties should shift their focus and energy toward tackling this problem.

Competing In The Age Of AI Is Simpler Than You Think

By Sophia Matveeva

Artificial Intelligence is the new fashionable trend in business. While many large corporates create skunkworks for experimental technologies or acquire startups, few incumbent businesses have allowed AI processes to change the core of the organization. This could be because executives in traditional businesses have little understanding of how these technologies work and are unwilling to take the risk of investing in something they do not understand.

A recent book by two Harvard Business School professors attempts to deal with this issue. Competing in the Age of AI: strategy and leadership when algorithms and networks run the world presents a compelling case for putting AI at the center of the business. Any business.

Authors Marco Iansiti and Karim R. Lakhani show the example of Ant Financial, which serves more than 10 times as many customers as the largest U.S. banks with less than one tenth the number of employees. That extraordinary combination of wide reach and low cost is possible because Ant Financial uses data and artificial intelligence from its core mobile payments platform, Alipay.

While Alibaba and its offspring were digital first companies, Iansiti and Lakhani argue that these capabilities are available to traditional businesses and are not as alien as they might first appear.

Artificial intelligence that mimics human emotion and creativity captures the imagination and ignites fear. Yet, synthetic companions like Star Trek’s Commander Data are still in the distant future.

However, weak AI is the force that is upending industries today. In a recent Harvard Business Review post, the authors argued that “the AI that can drive the explosive growth of a digital firm often isn’t even that sophisticated.” As long as a computer can perform tasks traditionally handled by people, a company can drive significant benefit.

Weak AI manages key business processes and operating decisions. A simple example of this is warehouse robots used by delivery firms like Amazon and Ocado, where robots rather than people collect items in huge warehouses.

Becoming AI centric

While even this sounds expensive, becoming AI centric is actually even simpler. First, organizations need to agree to put software at the core of the firm, rather than people.

The authors argue that creating an “AI factory” at the core of the firm consists of four components: the data pipeline, algorithms, experimentation to test these algorithms and infrastructure to connect these technical processes.

This is as true for Uber as it is for Ocado. While getting a taxi and eating an organic banana are different consumer experiences, the process that brings them to customers is the same.

Companies do not have to hire swathes of statistics PhDs to get started. Existing commercial teams can start by deciding what data to collect and creating hypotheses to test. For example, you could begin by asking: what assumptions do you have about your best customers? How can you test them?

A big career opportunity

Artificial intelligence, machine learning and data science present big opportunities for technical and non-technical professionals alike. According to the LinkedIn Emerging Jobs report, machine learning engineer and data scientist are both in the top 20 fastest growing professions.

However, LinkedIn’s principal economist Guy Berger says, “you cannot outsource decisions just to the tech people.” While retraining to become a data scientist may not make the best use of many people’s talents, understanding basic technology processes is a job requirement for ambitious professionals.

The good news is that learning basic processes about how technology products are made or how data is analysed is not difficult. My favourite subject at college was Ancient Greek theater, yet I have participated in designing algorithms. I do not write the code, but I work on the assumptions our company wants to test and the behavior we want the algorithm to encourage.

In Competing in the Age of AI, Iansiti and Lakhani have made AI accessible to non-technical professionals and shown how simple processes can make a big difference. This is a useful book to begin what could be an interesting and lucrative journey. ( Source: Forbes)

Novel formulation permits use of toxin extracted from rattlesnake venom to treat chronic pain

By Chloé Pinheiro | Agência FAPESP – Crotoxin, extracted from the venom of the South American rattlesnake Crotalus durissus terrificus, has been studied for almost a century for its analgesic, anti-inflammatory and antitumor activities and as an even more powerful muscle paralyzer than botulinum toxin. However, the toxicity of crotoxin limits its medicinal use.

A new study, published by Brazilian researchers in the journal Toxins, shows that crotoxin’s therapeutic effects can be enhanced and its toxicity reduced when it is encapsulated in nanostructured SBA-15 silica, a material originally developed for use in vaccine formulations.

The study was conducted under the aegis of Brazil’s National Science and Technology Institute (INCT) on Toxins, one of the INCTs supported by FAPESP in São Paulo State in partnership with the National Council for Scientific and Technological Development (CNPq), an agency of the Brazilian government. The INCT’s principal investigator is Osvaldo Augusto Sant’Anna.

The study was part of the doctoral research of Morena Brazil Sant’Anna, whose thesis advisor is Gisele Picolo. Picolo herself was the principal investigator for a project on the same topic. Researchers Flavia Souza Ribeiro Lopes and Louise Faggionato Kimura participated in the study, which was performed at Butantan Institute in São Paulo.

Osvaldo Sant’Anna is the principal investigator for a Thematic Project at Butantan Institute to study mesoporous silica as a vaccine adjuvant in collaboration with Márcia Fantini, a professor at the University of São Paulo’s Physics Institute (IF-USP). An adjuvant is an agent used in conjunction with a vaccine antigen to augment the host’s antigen-specific immune response.

“People who respond badly to vaccines usually have macrophages that catabolize the antigen very quickly, so there isn’t time for their lymphocytes to induce a complete response in terms of producing antibodies,” Osvaldo Sant’Anna told Agência FAPESP. “Research has shown that nanostructured silica slows the macrophages down.”

Osvaldo Sant’Anna’s studies show that mice produce more antibodies against an antigen when it is administered with silica, which is made up of microstructures and can be molded to encapsulate molecules of varying shapes and sizes.

When silica was tested with other toxins, a novel protective effect was discovered. “In tests conducted in horses to produce anti-diphtheria serum and with tetanus toxin, we found that silica makes antigens less potent and reduces the adverse effect of diphtheria toxin,” Osvaldo Sant’Anna said.

These findings were welcomed by Picolo and Morena Brazil Sant’Anna, colleagues of Osvaldo Sant’Anna at Butantan Institute. “I’ve been studying crotoxin since 2011. The results are positive in terms of its analgesic effect, but its toxicity has always been a constraint. Using silica was a great idea. This is the first time the two molecules have been combined,” Picolo said.

Neuropathic pain

The article published in Toxins reports on a study designed to investigate the effects of crotoxin combined with SBA-15 silica when used to treat neuropathic pain, a chronic condition caused by injuries to sensitized nerves. Treating chronic pain is a challenge for physicians because ordinary painkillers such as anti-inflammatory drugs and opioids do not have the desired effect.

To evaluate crotoxin’s therapeutic potential in this setting, the researchers conducted experiments with mice, inducing a condition similar to neuropathic pain by injuring the sciatic nerve.

The first positive finding resulted from a test to determine the maximum dose of crotoxin with and without silica. “We observed that a larger amount of the toxin combined with silica could be administered without adverse side effects and that the dose could therefore be increased,” Morena Brazil Sant’Anna said. It was possible to administer a 35% larger dose of crotoxin when it was combined with silica.

The next step was to test the formulation in animals. They were given the crotoxin/silica complex (CTX:SBA-15) while experiencing acute pain (immediately after a sciatic nerve injury procedure) or chronic pain (a fortnight later). In both cases, the complex was administered in a single dose or in five doses (one daily dose for five consecutive days).

In the acute stage as well as the chronic stage, the analgesic effect lasted longer when crotoxin was combined with silica. In one of the tests, a single dose was sufficient to reverse hypernociception (heightened sensitivity to painful stimuli) until 48 hours after it was administered.

Action mechanisms

Crotoxin is a powerful painkiller because it acts on different pain pathways. To determine whether its action mechanisms would be the same in the new formulation, the researchers administered antagonists of the receptors involved in pain shortly before the crotoxin/silica complex. If the complex was effective even with the receptors blocked, this would mean its action mechanism could be different from that of the conventional molecule.

“We found that muscarinic and adrenergic receptors, which act on the nervous system, and formyl receptors, which are targets for natural anti-inflammatory compounds, were involved in the action of the crotoxin/silica complex. In other words, there was no change in the action mechanism,” Morena Brazil Sant’Anna said.

The team observed changes in the levels of pro- and anti-inflammatory cytokines. “Expression of interleukin 6 [IL-6], which is associated with inflammation, decreased, while the level of IL-10, which controls the inflammatory process, increased. We also observed a reduction in activation of astrocytes and microglia, central nervous system cells involved in inflammatory responses,” Picolo said.

Because silica influences the immune response, the researchers decided to see whether the defense against toxicity it triggers would end up hindering crotoxin’s beneficial action. This possibility was tested and ruled out in the study. The mice produced high levels of antibodies, but this did not affect the outcome, according to Picolo. “Probably because the crotoxin was encapsulated and the antibodies produced were unable to reach it,” she said.

The complex gains another advantage from this protection: it could be administered orally to mice, for the first time, with positive results. This was possible because the structure of SBA-15 is similar to that of a honeycomb, protecting the active ingredient against breakdown in the stomach.

“It also guarantees controlled release of the crotoxin in the organism, which may explain the lasting analgesic effect,” Picolo said.

Next steps

The researchers are now investigating whether the combination of crotoxin with SBA-15 can be used to treat multiple sclerosis. The results of this research have also been positive so far, and an article will soon be published.

However, more studies will be necessary before the combination can become medication. “Crotoxin is a large molecule with a complex structure that’s hard to replicate in the laboratory, so scaled-up use is a long away off,” Picolo said.

Some form of synthesis would be the ideal solution. Trials are currently ongoing with purified venom extracted directly from the rattlesnake.