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St. Petersburg University scientists create new assembler for viral genome deciphering

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Researchers at St. Petersburg State University – the alma mater of Russian President Vladimir Putin – continue their battle with the coronavirus infection and are coming up with ever new tools that will help defuse not only COVID-19, but its counterparts as well. Bioinformatics experts at St. Petersburg State University’s Center for Algorithmic Biotechnology, together with their colleagues from University of California at San Diego, have unveiled the metaviralSPAdes assembler – a new collector that makes it possible to single out and put together the viral genome from among many other sequences. This will help decipher the genomes of pathogens faster and more conveniently, thus making it possible to expedite the development of test systems and vaccines against dangerous infections. There is a scientific article to this effect published in the journal Bioinformatics.

When humanity is faced with a new virus, the first thing biologists do is to try to decipher its genome to diagnose the disease and develop a vaccine. However, if sequencing has to be done amid the outbreak of a new pathogen, a problem arises. For example, the saliva of a patient with COVID-19, which was used for the very first decoding of the SARS-CoV-2 coronavirus, contained the genomes of many other, mostly harmless viruses. Not to mention the hundreds of bacteria living in the human mouth and complicating the search for viral sequences.

This example shows the importance of being able to solve a much more complex computational problem than deciphering a single genome, namely to collect metagenomes, sets of hundreds of different genomes of microorganisms living in the same environment. The problem is, however, that as a result of such work, thousands of sequences can be obtained that may include fragments of the genetic code of both viruses and bacteria, which make it hard to understand exactly which data belongs to the desired pathogen.

In addition, scientists will inevitably be faced with another task – the sequencing of metavirome in order to identify exactly the viral sequences hiding among much longer bacterial sequences. This done, bioinformatics experts will be able to stitch together, literally piece by piece, the complete genome of the virus that has caused the outbreak.

Until recently, researchers lacked the special tool to collect viral metagenomes, but a team of Russian and US scientists from St. Petersburg State University and University of California at San Diego has developed a metaviralSPAdes assembler, which significantly facilitates the analysis of the results of metavirome sequencing.

Biologists are still unable to read the entire genome in the same way as we read a book: from beginning to end. Instead, they read small snippets of a genome, that’s why assembling the genome does not differ much from putting together a puzzle of a million fragments. Oftentimes, this task is considered as one of the most complex algorithmic problems in bioinformatics. And still, it can still be solved. For example, the most widely used genomic assembler SPAdes (Saint Petersburg Assembler), also created by the Russian-American team of scientists, has already been used in almost 9,000 studies. It helped scientists analyze the pathogens that caused the outbreak of the Middle East Respiratory Syndrome (MERS) in Saudi Arabia, Ebola in Congo, gonorrhea in England, meningitis in Ghana, dengue fever in Sumatra and dozens of other outbreaks that have happened over the past eight years since SPAdes came along.

It should also be noted that assembling a metagenome from 1,000 genomes is way more difficult than lumping together a single genome sequence. Here you have to deal with 1,000 individual puzzles instead of one: you need to put together a “picture,” whose fragments are mixed with billions of pieces from other puzzles. To solve this problem, three years ago, the same Russian-US team of scientists who created SPAdes, developed the metaSPAdes assembler, which, in turn, became the leading metagenomic assembler. It made the extraction of viral sequences from a huge amount of data much easier, but the metaviral SPAdes assembler of the new generation is able not only to locate fragments of viral genomes, but also to assemble them into a ready-made “puzzle” – the pathogen genome.

The COVID-19 pandemic came as a wake-up call for biologists studying animal-to-human transmission of viruses, and reminded us of the importance of studying different carriers of this virus, such as bats, who boast a one-of-a-kind immune system allowing them to live with multiple pathogens that are lethal to humans. We need to know the nature of the diseases they catch before, not after a pandemic strikes.

Counting the viral genomes of various animals is not an easy task, of course, but with the creation of metaviral SPAdes, biologists will now find it much easier to reconstruct the viral genomes of bats or any other potential sources of future pandemics.

Taking part in the development of the new genomic collector were researchers from the Center for Algorithmic Biotechnology of St. Petersburg State University’s Institute of Translational Biomedicine Dmitry Antipov and Mikhail Raiko, the Center’s Deputy Director, St. Petersburg State University Professor Alla Lapidus, and Pavel Pevzner, Professor at University of California at San Diego and a world-acclaimed expert in bioinformatics. Earlier, scientists at St. Petersburg State University’s Center for Algorithmic Biotechnology helped their colleagues from the Smorodintsev Research Institute of Influenza to decipher, for the first time, the genome of the “Russian” variant of the SARS-CoV-2 virus, which led to the COVID-19 pandemic. On March 15, 2020 they managed to extract the viral RNA froma swab sample obtained from an infected resident of St. Petersburg. Recently, an international team of scientists, led by Pavel Pevzner, developed a novel computational method of detecting cyclopeptides, a class of substances that includes many well-known antibiotics. Using a method, called CycloNovo, the scientists have found 79 new potential candidates for the role of bacteria killers.

Slavisha Batko Milacic is a historian and independent analyst. He has been doing analytics for years, writing in Serbian and English about the situation in the Balkans and Europe. Slavisha Batko Milacic can be contacted at email: varjag5[at]outlook.com

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Implementation of virtual reality and the effects in cognitive warfare

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Photo: Lux Interaction/Unsplash

With the increasing use of new technologies in warfare situations, virtual reality presents an opportunity for the domain of cognitive warfare. Nowadays, cognitive skills are treated equally as their physical counterparts, seeking to standardize new innovative techniques. Virtual reality (VR) can be used as a tool that can increase the cognitive capabilities of soldiers. As it is understandable in today’s terms, VR impacts the brain directly. That means that our visual organs (eyes) see one object or one surrounding area, but brain cells perceive and react to that differently. VR has been used extensively in new teaching methods because of the increased probability of improving the memory and learning capabilities of students.

Besides its theoretical teaching approach and improvement of learning, VR can be used systematically towards more practical skills. In medicine for example students can have a full medicine lesson on a virtual human being seeing the body projected in 3D, revolutionizing the whole field of medicine. If that can be used in the medical field, theoretically it will be possible to be used in combat situations, projecting a specific battlefield in VR, increasing the chances of successful engagement, and reducing the chance of casualties. Knowing your terrain is equally important as knowing your adversary.

The use of VR will also allow us to experience new domains relating to the physical health of a person. It is argued that VR might provide us with the ability to effectively control pain management. Since VR can stimulate visual senses, then it would be safe to say that this approach can have higher effectiveness in treating chronic pain, depression, or even PTSD. The idea behind this usage is that the brain itself is already powerful enough, yet sometimes when pain overwhelms us we tend to lose effectiveness on some of our senses, such as the visual sense. An agonizing pain can blurry our vision, something that we cannot control; unless of course theoretically, we use VR. The process can consist of different sounds and visual aids that can trick the mind into thinking that it is somewhere that might be the polar opposite of where it is. Technically speaking, the mind would be able to do that simply because it works as a powerful computer, where our pain receptors can override and actually make us think that we are not in such terrible pain.

Although the benefits of VR could be useful for our health we would still need to deal with problems that concern our health when we use a VR set.  It is possible that the brain can get overloaded with new information and the new virtual environments. VR poses some problems to some people, regarding the loss of the real environment and creating feelings of nausea or extreme headaches. As a result, new techniques from cognitive psychologists have emerged to provide a solution to the problem. New technologies have appeared that can desaturate colors towards the edge of the headset in order to limit the probability of visual confusion. Besides that, research shows that even the implementation of a virtual nose when someone wears a VR headset can prevent motion sickness, something that our brain does already in reality.

However, when it comes to combatants and the implementation of VR in soldiers, one must think of maybe more effective and fast solutions to eliminate the problems that concern the confusion of the brain. Usage of specific pharmaceuticals might be the key. One example could be Modafinil which has been prescribed in the U.S. since 1998 to treat sleep-related conditions. Researchers believe it can produce the same effects as caffeine. With that being said, the University of Oxford analyzed 24 studies, where participants were asked to complete complex assignments after taking Modafinil and found out that those who took the drug were more accurate, which suggests that it may affect higher cognitive functions.

Although some of its long-term effects are yet to be studied, Modafinil is by far the safest drug that can be used in cognitive situations. Theoretically speaking, if a long exposure to VR can cause headaches and an inability to concentrate, then an appropriate dose of Modafinil can counter the effects of VR. It can be more suitable and useful to use on soldiers, whose cognitive skills are better than civilians, to test the full effect of a mix of virtual technology and pharmaceuticals. VR can be a significant military component and a simulation training program. It can provide new cognitive experiences based on foreign and unknown terrains that might be difficult to be approached in real life. New opportunities arise every day with the technologies, and if anyone wanted to take a significant advantage over adversaries in the cognitive warfare field, then VR would provide a useful tool for military decision-making.

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Vaccine Equity and Beyond: Intellectual Property Rights Face a Crucial Test

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The debate over intellectual property rights (IPRs), particularly patents, and access to medicine is not new. IPRs are considered to drive innovation by protecting the results of investment-intensive R&D, yet arguably also foster inequitable access to affordable medicines.

In a global public health emergency such as the COVID-19 pandemic, where countries face acute shortages of life-saving vaccines, should public health be prioritized over economic gain and the international trade rules designed to protect IPRs?

The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPs), to which all 164 member states of the World Trade Organization (WTO) are a party, establish minimum standards for protecting different forms of IPRs. 

In October 2020, India and South Africa – countries with strong generic drug manufacturing infrastructure – invoked WTO rules to seek a temporary waiver of IPRs (patents, copyrights, trade secrets, and industrial designs) on equipment, drugs, and vaccines related to the “prevention, containment or treatment of COVID-19.” A waiver would mean that countries could locally produce equipment and vaccines without permission from holders of IPRs. This step would serve to eliminate the monopolistic nature of IPRs that give exclusive rights to the holder of IPRs and enable them to impose procedural licensing constraints.

Brazil, Japan, the European Union (EU), and the United States (US) initially rejected the waiver proposal. That stance changed with the rise of new COVID-19 mutations and the associated increase in deaths, with several countries facing a public health crisis due to vaccine supply shortages. The position of many states began shifting in favor of the India-South Africa proposal, which now has the backing of 62 WTO members, with the US declaring support for the intent of the temporary waiver to secure “better access, more manufacturing capability, more shots in arms.” Several international bodies, the World Health Organization (WHO), and the UN Committee on Economic, Social and Cultural Rights have voiced support.

Some countries disagree about the specific IPRs to be waived or the mechanisms by which IPRs should be made available. The EU submitted a proposal to use TRIPS flexibilities such as compulsory licensing, while others advocate for voluntary licensing. The TRIPS Council is conducting meetings to prepare an amended proposal to the General Council (the WTO’s highest-level decision-making body in Geneva) by the end of July 2021.

The crisis in India illustrates the urgency of the situation. India produces and supplies Covishield, licensed by AstraZeneca; and Covaxin, which is yet to be included on the WHO’s Emergency Use Listing (EUL). Due to the devastating public health crisis, India halted its export of vaccines and caused a disruption in the global vaccine supply, even to the COVID-19 Vaccines Global Access (COVAX) program. In the meantime, the world’s poorest nations lack sufficient, critical vaccine supplies.

International law recognizes some flexibility in public health emergencies. An example would be the Doha Declaration on TRIPS and Public Health in 2001, which, while maintaining the commitments, stresses the need for TRIPS to be part of the wider national and international action to address public health problems. Consistent with that, the body of international human rights law, including the International Covenant on Economic, Social and Cultural Rights (ICESCR), protects the right to the highest attainable standard of health.

But as we race against time, the current IPR framework may not allow for the swift response required. It is the rigorous requirements before a vaccine is considered safe to use under Emergency Use Authorizations and procedural delays which illuminate why IPR waivers on already approved vaccines are needed. Capitalizing on the EUL’s approved vaccines that have proven efficacy to date and easing IPR restrictions will aid in the timely supply and access of vaccines.

A TRIPS waiver may not solve the global vaccine shortage. In fact, some argue that the shortages are not an inherent flaw in the IP regime, considering other supply chain disruptions that persist, such as the ones disrupting microchips, pipette tips, and furniture. However, given that patent licensing gives a company a monopoly on vaccine commercialization, other companies with manufacturing capacity cannot produce the vaccine to scale up production and meet supply demands.

Neither does a temporary waiver mean that pharmaceutical companies cannot monetize their work. States should work with pharmaceuticals in setting up compensation and insurance schemes to ensure adequate remuneration.

At the College of Law at Hamad Bin Khalifa University, our aim is to address today’s legal challenges with a future-oriented view. We see COVID-19 as a case study in how we respond to imminent and existential threats. As global warming alters the balance of our ecosystem, threats will cascade in a way that is hard to predict. When unpredictable health emergencies emerge, it will be human ingenuity that helps us overcome them. Even the global IP regime, as a legal system that regulates ideas, is being tested, and should be agile enough to respond in time, like the scientists who sprang into action and worked tirelessly to develop the vaccines that will soon bring back a semblance of normal life as we know it.

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Sputnik V in the International Arena

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Over a year since the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic in March 2020, the disease is far from under control. Although global case rates on the whole have declined, 15 countries remain near or at the peak of their infection curve. Even countries well below their peak daily infection rates – such as the United Kingdom and Morocco – recently have witnessed an uptick in cases. Just this summer, the virus’ global death toll surpassed 4 million. Fortunately, scientists’ efforts to develop vaccines against COVID-19 have been fruitful: 16 vaccines have been either authorized for emergency use or fully approved. Russia’s Sputnik V is one of the most effective of them, yet one of the most controversial as well.

An important tool in humankind’s fight against the pandemic, Sputnik V is being overlooked by western powers on political grounds.

Sputnik V: controversy and advantages

Much of the controversy surrounding the Gamaleya Institute’s vaccine in western media and political discourse stems from the details surrounding Sputnik V’s approval. Russia’s Ministry of Health issued a registration certificate for the vaccine on August 11, 2020, thus making Sputnik V the world’s first vaccine to be granted regulatory approval for use against COVID-19. Instead of igniting international celebration, this development was met largely with skepticism as many considered the move premature. Typically, vaccines undergo extensive Phase 3 trials before government authorization for use. Sputnik V’s Phase 3 trials, however, did not begin until September 2020, after the vaccine had been registered. Since then, the Russian Ministry of Health’s unorthodox approach to approving the vaccine has been weaponized against Sputnik V.

Western media has also repeatedly called into question Sputnik V’s efficacy and safety. A study in the respected, peer-reviewed medical journal the Lancet, however, found that Sputnik V has an efficacy rate of 91.6% and is low-risk. Although a group of scientists raised concerns about the study’s integrity citing lack of transparency, no major scientific studies demonstrating that Sputnik V’s efficacy is significantly lower than reported have been published to date. Respected western media sources, such as the New York Times and the BBC, cite the Lancet’s figure when reporting on Sputnik V’s efficacy. Meanwhile, a report by the Argentinian Ministry of Health found that Sputnik V is one of the safest vaccines widely used in Argentina. As summarized in the Lancet: “the development of the Sputnik V vaccine has been criticised for unseemly haste, corner cutting, and an absence of transparency. But the outcome reported here is clear and the scientific principle of vaccination is demonstrated, which means another vaccine can now join the fight to reduce the incidence of COVID-19.”

Regardless of such controversy, the vaccine has several key advantages – namely its efficacy, affordability, and transportability. Sputnik V is one of only three vaccines globally with an efficacy of over 90% – the other two being Pfizer-BioNTech and Moderna. Running at less than $10 per dose on international markets, Sputnik V is the cheapest vaccine in this efficacy range. For comparison, the Pfizer-BioNTech vaccine runs between $14.50 and $20.00 on international markets, while Moderna’s vaccine sells for between $18.00 and $33.00 a dose. Sputnik V is also much easier to transport than its U.S./German counterparts. The Pfizer-BioNTech and Moderna vaccines must be stored at -70.0°C and -20.0°C respectively, whereas Sputnik V must be kept at a temperature range from 2 to 8°C, meaning that it can be stored in conventional refrigerators. This makes delivering the vaccine notably easier, especially to remote areas. Thus, Sputnik V is poised to make an important contribution to the global inoculation campaign.

Hurdles and victories in the international arena

Russia’s frontrunner vaccine has experienced a mix of hurdles and victories in the international arena. The biggest hurdles are regulatory in nature. For example, one major obstacle preventing the vaccine’s distribution is that the European Medicines Agency (EMA) – the EU agency responsible for authorizing and evaluating medicines – has not yet approved Sputnik V. The EMA is still undergoing its rolling revue of the vaccine, and it appears that approval is unlikely to be granted until September at the earliest. Italian Prime Minister Mario Draghi recently raised the possibility that Sputnik may never get the EMA’s approval, casting further doubt on the vaccine’s future in Europe. The EMA’s regulatory hesitancy towards Sputnik V has prevented major EU players, such as Germany and France, from buying millions of doses of the vaccine.

Sputnik V similarly has not yet been cleared for Emergency Use Listing by the WHO. The UN agency found production violations at the Sputnik V manufacturing site in Ufa during a June examination. Although the WHO’s concerns have since been addressed according to Russian Press Secretary Dmitry Peskov, the incident has further put on hold the Russian Direct Investment Fund’s (RDIF) commitment to supply the United Nations International Children’s Emergency Fund with 220 million doses of Sputnik V. In a similar vein, the RDIF applied for Sputnik V to participate in COVID-19 vaccine access program COVAX earlier this year. Discussions with the Vaccine Alliance Gavi regarding Sputnik V’s inclusion in the COVAX Facility’s Portfolio of COVID-19 vaccines, however, are still ongoing.

Although Sputnik V’s lack of EMA and WHO approval has hampered its international rollout, the ongoing authorization process has not eliminated the vaccine’s global relevance. In fact, the Russian vaccine is currently authorized for emergency use in nearly 70 countries and being used in 45. Two EU member states, Hungary and Slovakia, even have begun inoculating their citizens with Sputnik V without a greenlight from the EMA. Meanwhile, India and Turkey have ordered 250 million and 50 million doses of the vaccine, respectively. One thing is clear: Sputnik V is in high demand internationally despite the regulatory hurdles and controversies it faces. Trust in the Russian vaccine also remains markedly high notwithstanding these challenges. A poll conducted by British market research firm YouGov during February and March of this year found that, of participants who had a preference, 54.0% trusted Russia to produce a vaccine and 33.2% preferred to be vaccinated with Sputnik V. According to the survey, Russia and the United States are tied for the most trusted vaccine producing country, and Sputnik V is the second most preferred vaccine after Pfizer-BioNTech, which 36.6% of respondents favored. The survey featured respondents from the following 9 countries, collectively accounting for 25% of the global population: India; Brazil; Mexico; the Philippines; Vietnam; Argentina; Algeria; the UAE; and Serbia.

Sputnik V has been particularly successful in Latin America, a core region of the United States’ sphere of influence. Repeated polling has shown that Sputnik V enjoys high levels of confidence in Latin American countries, especially Argentina and Peru. The Russian vaccine got an early start in the region when on December 29, 2020, Argentina became the first Latin American country to administer the Sputnik V vaccine to its citizens. Mexico followed suit on February 24 and Nicaragua on March 2, 2021. To the surprise of many observers, on June 4 Brazil joined the list of countries that have approved Sputnik V.

Unfortunately, alongside the success Sputnik V has experienced in Latin America, the vaccine has also encountered a substantial challenge: supply shortages. Both Mexico and Argentina are currently facing shortages of Sputnik V’s second dose – and the problem is not confined to the region. Luckily, Russia’s strategy for eliminating supply shortages not only promises to see more people vaccinated, but also provides an opportunity for Russia to collaborate with its international partners: the country will manufacture vaccines abroad. Starting in July, 5 to 6 million doses of Sputnik V are set to be produced outside of Russia per month. Manufacturing countries include India, South Korea, and Brazil. The Argentine laboratory Richmond produced its first half million doses on June 18. The data sharing and collaboration necessary to manufacture Sputnik V abroad have the potential to increase Russia’s soft power in partner countries.

The other major players

It is crucial to note that Russia’s Sputnik V is only one piece in the puzzle of fighting COVID-19. Although an in-depth review of every country’s current approach to vaccine policy is beyond the scope of this article, a brief overview of the major vaccine providers’ – the United States, the United Kingdom, and China – global vaccine distribution is in store.

Unlike Russia, whose approach to vaccine distribution has been global facing since Sputnik V’s development, the United States initially favored domestic distribution and stockpiling of American vaccines. The Biden Administration has since turned course. The U.S. recently pledged to share 80 million U.S. vaccine doses by the end of June and to purchase 500 million additional doses of the Pfizer-BioNTech vaccine for lower-income countries over the next year. Pfizer-BioNTech is currently being distributed in 105 countries, Moderna in 55, and Johnson&Johnson in 27.

The United Kingdom’s Oxford-AstraZeneca vaccine is currently being used in 178 countries, making it the most widely-used COVID-19 vaccine to date. Although evidence that the vaccine is linked to blood clots put a rut in its distribution, the vaccine is performing well internationally. Meanwhile, China’s Sinopharm-Beijing and Sinovac vaccines are being used in 40 and 32 countries, respectively. China has favored international distribution of its vaccines since the beginning of the pandemic and has shipped more vaccines abroad than any other country. The vaccines referenced in this article – among others – have collectively led to 22.2% of the world’s population having received at least one dose of a COVID-19 vaccine.

Conclusion

Western, especially American, media has portrayed Sputnik V in an overwhelmingly negative light. The Russian vaccine is represented more as a political tool than a health solution. Hiccups in the road to Sputnik V distribution are cited as evidence that the vaccine is not to be trusted. This approach to Sputnik V is fundamentally flawed. Regulation and safety inspections are crucial to safe vaccination efforts; finger-pointing and name-calling are not. Ultimately, vaccination should take precedence over politics. Alongside other vaccines, Sputnik V will propel us into a post-pandemic world.

Above all else, Sputnik V is a highly efficacious vaccine against COVID-19. When Sputnik V successfully performs its function – safely preventing vaccinated people from contracting and dying from the virus – a growth in vaccinated individuals’ trust of Russia will organically follow. This happy side effect undoubtedly has the potential to promote Russia’s image abroad and increase the country’s soft power. But even if Russia’s political gains from Sputnik V turn out to be small, humankind’s gains in lives saved will be immeasurable.

From our partner RIAC

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