6:35 AM 7/9/2020 - Researchers map RNA structure throughout SARS-CoV-2 genome
- Get link
- Other Apps
Researchers map RNA structure throughout SARS-CoV-2 genome https://www.news-medical.net/news/20200709/Researchers-map-RNA-structure-throughout-SARS-CoV-2-genome.aspx …
6:35 AM 7/9/2020
Michael Novakhov - SharedNewsLinks℠ | InBrief |
|Michael Novakhov - SharedNewsLinks|
|Researchers map RNA structure throughout SARS-CoV-2 genome|
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is currently at the heart of a pandemic that has cost the world more than 550,000 lives, 12 million infections, and uncounted years of productivity, is an RNA virus with the largest genome among all such viruses. This 30 kb size virus has caused many difficulties for scientists in search of a vaccine.
Novel Coronavirus SARS-CoV-2 This scanning electron microscope image shows SARS-CoV-2 (round gold objects) emerging from the surface of cells cultured in the lab. SARS-CoV-2, also known as 2019-nCoV, is the virus that causes COVID-19. The virus shown was isolated from a patient in the U.S. Image captured and colorized at NIAID's Rocky Mountain Laboratories (RML) in Hamilton, Montana. Credit: NIAID
What the RNA DoesThe RNA in the viral genome is the template for translation of a complex array of enzymes that builds up the viral transcriptome a set of subgenomic RNA sequences that encodes all the other components of the viral particle. This includes highly conserved bits of RNA that stay the same across strains and even families, probably because they are so important in viral replication. These structural elements with high functionality have been little explored in the SARS-CoV-2.
Previous reports have suggested that this virus also forms genome-scale ordered RNA structures (GORS) like other coronaviruses. This feature confers fitness and persistence. Since RNA structure is essential for viral function and for higher-order compaction, the current study focuses on this aspect of the viral genome.
Comparing RNA Secondary StructuresIn a new study out of Yale University and published on the preprint server bioRxiv* researchers assessed the folding stability of the RNA genome of this virus in comparison to other known systems, to explore the biological contributions made by these structural features. Despite the size, they aimed to produce a broad landscape of the overall as well as detailed structure and organization of the virus, which would help to identify those regions that had the most potential for regulating its life cycle.
The study conducted a comparative structural analysis of SARS-CoV-2 genomic RNA as well as of the previously known most highly structured RNA virus, the hepatitis C virus (HCV), the West Nile virus which is considered to be lacking overall RNA structure, and a set of human mRNAs which do not have internal structure.
They use what is called a Z-score to assess the tendency to form stable RNA structures. Negative Z-score values suggest the presence of very stable secondary structures in the RNA. This was -0.35 (median) for the human mRNAs, and -0.2 for the West Nile virus, suggesting low base pairing. On the other hand, the Z-scores for the HCV genome were almost always -1 throughout, showing that the tendency to form base pairs was high throughout the genome.
The SARS-CoV-2 shows a much more negative Z score distribution, showing its much higher tendency towards stable base pairings leading to the formation of more secondary structures, much more than any other RNA analyzed so far and not explicable as a coincidence. The median value of -1.5 shows it is likely to form a large and intricate pattern of functional secondary structures in coding and non-coding regions of its functional domains.
Distributions of Z-scores for the RNA genomes of SARS-CoV-2, HCV and West Nile viruses and a composite of human mRNAs. The bar plots are frequency distributions (y-axis) of free-energy Z-scores (x-axis) calculated in sliding windows tiling each RNA. Each histogram is overlaid with a Gaussian (normal distribution) fit represented by a solid blue curve.The study shows that the RNA folding stability of this genome is twice that of the HCV, hitherto the hallmark of stable secondary structure. This complex structure is biologically very significant.
Developing Platforms for Base Pair QuantificationThey constructed a workflow and the tools to decipher the base pair content from the secondary structure of any long RNA as well as to pick up any structural definition in a transcript containing kb of base pairs. Using this, they identified the highly complex structural regions of RNA, so as to compare predicted structures among the domains of this large RNA.
They saw that the genome was mostly folded into stable and separate repeating structural elements or motifs, with the base pair content (BPC) being about 61% on average, which is in keeping with the Z-score. There are abundant stable secondary and tertiary well-defined structural regions within the genome.
Distribution of well-defined RNA structures across the SARS-CoV-2 genome. (A) The percentage of nucleotides in well-defined structured regions (high BPC/low Shannon) was calculated in 100-nt bins tiling the genome and is plotted as a function of the genomic coordinate (gray curve). Individual percentages of each genomic bin are also represented as a heatmap in the same graph (color legend on the top right-hand corner). A scheme representing the genomic divisions of SARS-CoV-2 is shown next to the plot to guide the location of structured regions. (B) An expanded view of the initial two-thirds of the genome from the graph in (A) is shown along with the genomic divisions of this region (UTR + ORF1ab and corresponding NSP divisions). (C) The downstream third of the genome is expanded from the graph in (A) to zoom in on individual structural and accessory ORFs in this region.
Specific Regions of Highly Structured RNAThe result was that they found that both the untranslated regions, at the 5 and 3 end, had a high level of structural content, at over 60% and 40% respectively, which can be explained as the presence of RNA regulatory elements responsible for viral replication and translation.
The ORF1ab that forms the upstream two-thirds of the genome has many foci of RNA structures non-uniformly distributed along the genome, with the Novel SH2-containing Protein (nsp) 1 segment, that is the most highly structured part, containing 56% of its nucleotides in clearly defined structures. In fact, the upstream part of the nsp1 segment is part of a large module that forms in conjunction with the 5 UTR, so that the upstream regulatory elements of the genome seem to overlap with the ORF considerably.
Other nsps form clusters of structural elements that are either confined within their respective domain limits or, as with nsp 4 to 6, 8 to 10, and 14-16, they may form structures that spill over the borders of the domain. This may mean that these RNA forms modules which are not always functional units. However, nsps 7 and 11 have no structured regions at all.
They also found a much higher number of structured regions among the open reading frames (ORFs), which code for structural and accessory proteins, and form the downstream one-third of the genome.
Genomic vs. Subgenomic StructuresThey also found that these ORF structures can shift depending on whether they are in a genome or a subgenomic fragment. For instance, they examined the nucleocapsid ORF, the most plentifully occurring subgenomic RNA that is found one order of magnitude more abundantly than any other. Because of the differences in the base-pairing potential when the N ORF is in the genome or separate from it, secondary structures that are formed in these contexts are different, and presumably, carry out different functions altogether. This could allow different levels of RNA stability, processing, and molecular functioning.
The Why and the Future of RNA Structural StudiesThe reason for such massive structuring could be protective, as this does not allow cellular nucleases to gain access to it and destroy it, allowing infection to continue. It may also enable immune evasion by minimizing the recognition patterns that can be picked up by pattern recognition receptors in the host cell. Thirdly, it allows distant elements of the large genome to interact by bringing them close to each other.
The study has thus brought out results that will provoke greater exploration of the complex ways in which viruses infect their hosts and how host responses occur. The uncovering of viral genomic structure could be immensely useful in finding new drug targets to aim at in the fight to develop a treatment for COVID-19.
The researchers conclude, The conclusions reported in this study provide a foundation for structure-function hypotheses in SARS-CoV-2 biology, and in turn, may guide the 3D structural characterization of potential RNA drug targets for COVID-19 therapeutics.
*Important NoticebioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
|Antonio Guterres on risks of bioterrorist attacks - Google Search|
<a href="http://economictimes.indiatimes.com" rel="nofollow">economictimes.indiatimes.com</a> News Defence
Apr 10, 2020 - The Secretary-General listed pressing risks to the world due to the pandemic as he addressed the powerful UN Security Council, which for the ...
COVID-19 pandemic reveals how bioterrorist attack may ...
www.livemint.com news india covid-19-pandemi...
<a href="http://www.livemint.com" rel="nofollow">www.livemint.com</a> news india covid-19-pandemi...
Apr 10, 2020 - Non-state groups could gain access to virulent strains that could pose similar devastation to societies around the globe, United Nations ...
COVID-19 threatening global peace and security, UN chief ...
news.un.org story 2020/04
<a href="http://news.un.org" rel="nofollow">news.un.org</a> story 2020/04
Apr 10, 2020 - While the COVID-19 pandemic is first and foremost a health crisis, its implications are more far-reaching and could threaten global peace and ...
UN Chief Warns of Deadly Germs as Potential Bioterrorist ...
www.ipsnews.net 2020/07 un-chief-warns-deadly-g...
<a href="http://www.ipsnews.net" rel="nofollow">www.ipsnews.net</a> 2020/07 un-chief-warns-deadly-g...
12 hours ago - Providing a grim economic scenario of the devastation caused by the pandemic UN chief Guterres warns of the possibility of an even worse ...
|Google Alert - sars cov 2 as bioweapon: UN Chief Warns of Deadly Germs as Potential Bioterrorist Weapons|
UNITED NATIONS, Jul 8 2020 (IPS) - The coronaviruswhich has claimed the lives of over 538,000 people and ... security issues, told IPS the use of a biological weapon would be an act involving the deliberate use of disease.
Google Alert - sars cov 2 as bioweapon
|UN Chief Warns of Deadly Germs as Potential Bioterrorist Weapons|
Armed Conflicts, Featured, Global, Global Geopolitics, Global Governance, Headlines, Health, IPS UN: Inside the Glasshouse, Peace, TerraViva United Nations
Credit: United NationsUNITED NATIONS, Jul 8 2020 (IPS) - The coronaviruswhich has claimed the lives of over 538,000 people and infected more than 11.6 million worldwidehas destabilized virtually every facet of human life ever since its outbreak in late December.
Providing a grim economic scenario of the devastation caused by the pandemic including rising poverty, hunger and unemployment UN Secretary-General Antonio Guterres warned last week of the possibility of an even worse disaster: the risks of bioterrorist attacks deploying deadly germs.
He said it has already shown some of the ways in which preparedness might fall short, if a disease were to be deliberately manipulated to be more virulent, or intentionally released in multiple places at once.
So, as we consider how to improve our response to future disease threats, we should also devote serious attention to preventing the deliberate use of diseases as weapons, he declared, speaking at a Security Council meeting on the maintenance of international peace and security and the implications of COVID-19.
Guterres pointed out that the Biological Weapons Convention (BWC), which codifies a strong and longstanding norm against the abhorrent use of disease as a weapon, has 183 States Parties.
I urge the 14 States that have not yet joined the Convention to do so without any further delay, he urged.
Opened for signature on April 10, 1972, the BWC entered into force on March 26, 1975, and currently has 183 states-parties.
Of the 14 countries outside the Convention, 10 have neither signed nor ratified the BWC, including Chad, Comoros, Djibouti, Eritrea, Israel, Kiribati, Micronesia, Namibia, South Sudan and Tuvalu, while four countries, Egypt, Haiti, Somalia and Syria, have signed but not ratified it.
John Loretz, a former Program Director and a senior consultant with International Physicians for the Prevention of Nuclear War (IPPNW) told IPS: I think the Secretary-General is absolutely correct in both assessments that the BWC is a strong treaty with widespread support, which needs to be strengthened, and that building up our public health institutions and pandemic response infrastructure would ensure that essential resources are in place should we ever have to deal with a biological weapons attack.
That said, one of the obstacles to getting effective oversight and verification into the BWCperhaps the biggest obstaclehas been lobbying by the biomedical and pharmaceutical industries and their allies, who have argued that its difficult to determine intent when assessing whether someone is using a toxin for legitimate reasons (e.g., vaccine development) or for prohibited reasons (i.e., weapons), and that intrusive inspections would compromise trade secrets and intellectual property rights.
Loretz said those who want to strengthen the BWC will have to find a way past industry stonewalling in order to give the treaty compliance tools such as those incorporated into the Nuclear Non-Proliferation Treaty (NPT) and the Chemical Weapons Convention (CWC).
Jez Littlewood, a freelance researcher with expertise in biological weapons, arms control, and national security issues, told IPS the use of a biological weapon would be an act involving the deliberate use of disease.
We know from consistent data about disease and its impacts worldwide that it can have potential devastating consequences.
The outbreak of Ebola in West Africa in 2014, the influenza pandemic of 1919 and the diseases brought by European explorers and settlers to the Americas from the 15th century onwards all had significant implications for populations, he noted, adding that 2017 data makes this clear: https://ourworldindata.org/causes-of-death
Tracing its history, Littlewood said bioterrorism certainly exists, but in the 25 years since Aum Shinrikyo launched its chemical weapons attack on the Tokyo subway system, bioterrorism has been low level and relatively unsophisticated.
Terrorists have killed far more people with vehicles, knives and basic firearms than they ever have with disease causing organisms, said Littlewood, who served under secondment to the UK Foreign and Commonwealth Office; and worked at the United Nations in Geneva.
John Hart, Non-Resident Scholar at the James Martin Center for Nonproliferation Studies, Monterey, California, told IPS it seems that the Secretary-Generals basic message is that preparedness against disease outbreaks also strengthens preparedness against so-called deliberate eventsnot that COVID-19 per se would be used as a method of warfare or for hostile purposes.
He pointed out that health infrastructures are fragile and societal resilience is weak. Therefore, international preparedness against biological warfare requires further strengthening.
And there are those who are working to strengthen the broader global architecture, he noted.
Credit: World Future FundLittlewood said it is correct to note that the barriers to creating a biological weapon are lower today than they were two decades ago, or even a decade ago, but deliberately causing a large-scale outbreak of a disease is far from easy.
He said States, rather than bioterrorists, are far more likely to have the technical, financial, and organizational capabilities to develop bioweapons of concern.
Deliberate manipulation for weaponization and multiple attacks requires capabilities no terrorist group has yet demonstrated it has, and no known group has demonstrated it has even come close to such a capability.
Littlewood also said that bioterrorism should not be dismissed, but empirical data from the last 25 years is clear in indicating there is far more interest in biological weapons among some terrorist groups than there is a capability to develop and use such weapons.
Purposefully manipulating the virulence of a disease-causing organism with a view to using it as a weapon is far more likely to be in the realm of a state-led program than a terrorist one, and features more prominently in Hollywood and fiction and political speeches than in reality, said Littlewood, who previously worked at Carleton University (Ottawa) and the University of Southampton (United Kingdom).
No state openly admits to or claims to have an interest in developing biological weapons, which speaks to the strength of the normative constraints on using disease deliberately as a weapon.
Nevertheless, Littlewood pointed out, a lack of preparedness of natural outbreaks of disease is a cause for concern and being prepared for natural outbreaks of disease is the foundation of any response to a deliberate use of a biological weapon.
Guterres said there is also need to strengthen the Convention, which lacks an oversight institution and contains no verification provisions, by enhancing its role as a forum for the consideration of preventative measures, robust response capacities and effective counter-measures.
Fortunately, the best counter to biological weapons is effective action against naturally occurring diseases. Strong public and veterinary health systems are not only an essential tool against COVID-19, but also an effective deterrent against the development of biological weapons, he added.
All of these issues must be on the agenda next year at the Conventions Review Conference, declared Guterres.
Asked if chemical weapons, used by warring factions in Syria, were categorized as biological weapons, Hart said both the BWC and the Chemical Weapons Convention cover toxins.
The allegations of use of weapons in Syria relate to chlorine, sarin and sulphur
mustard. These agents do not meet the definition of a biological weapon under the BWC, he declared.
The Syrian government carried out toxin research which it characterized as being defensive in nature.
This work is mentioned in Syrias declaration to the Organization for the Prohibition of Chemical Weapons (OPCW) and has been discussed at Executive Council meetings and at the margins of EC meetings, said Hart.
It is my understanding this particular matter is now largely resolved. The matter is referenced in statements, and some official public documentation, said Hart.
*Thalif Deen is a former Director, Foreign Military Markets at Defense Marketing Services; Senior Defense Analyst at Forecast International; and military editor Middle East/Africa at Janes Information Group.
He can be reached at email@example.com
|WHO Plans To Issue New Brief On Novel Coronavirus Modes Of Transmission Following Consultation With Scientists | KFF|
U.N. News: WHO to issue new brief on airborne transmission, following active engagement with scientists
The World Health Organization (WHO) is set to issue a brief on the modes of transmission of the new coronavirus, a senior official said on Tuesday. Epidemiologist Dr. Maria van Kerkhove, WHO technical lead on COVID-19, was responding to a journalists question about an open letter signed by hundreds of scientists urging the U.N. agency to update its recommendations on airborne transmission. Dr. van Kerkhove said WHO welcomes interaction with the scientific community (7/7).
Additional coverage of the expected brief is available from CNBC and New York Times.
|W.H.O. to Review Evidence of Airborne Transmission of Coronavirus|
After hundreds of experts urged the World Health Organization to review mounting scientific research, the agency acknowledged on Tuesday that airborne transmission of the coronavirus may be a threat in indoor spaces.
W.H.O. expert committees are going over evidence on transmission of the virus and plan to release updated recommendations in a few days, agency scientists said in a news briefing.
The possibility of airborne transmission, especially in crowded, closed, poorly ventilated settings, cannot be ruled out, said Dr. Benedetta Allegranzi, who leads the W.H.O.s committee on infection prevention and control.
She said the agency recommends appropriate and optimal ventilation of indoor environments, as well as physical distancing.
Agency staff fielded several questions from reporters about transmission of the virus by air, prompted by an open letter from 239 experts calling on the agency to review its guidance. Many of the letters signatories have collaborated with the W.H.O. and served on its committees.
We are very glad that W.H.O. has finally acknowledged the accumulating evidence, and will add aerosol transmission indoors to the likely modes of transmission for the coronavirus, said Jose-Luis Jimenez, a professor of chemistry at the University of Colorado Boulder. This will allow the world to better protect themselves and fight the pandemic.
In their letter, Dr. Jimenez and other scientists called on the W.H.O. to recommend that people avoid overcrowding, particularly on public transportation and in other confined spaces. Public buildings, businesses, schools, hospitals and care homes should also supply clean air, minimize recirculating air, and consider adding air filters and virus-killing ultraviolet lights, they said.
Public health agencies around the world take their cues from W.H.O., and hopefully this will lead to greater emphasis on wearing of face coverings and avoiding the three Cs: close contact, closed and poorly ventilated spaces, and crowds, said Linsey Marr, an aerosol expert at Virginia Tech. These measures will help slow the pandemic and save lives.
W.H.O. scientists said that for the past few months, the infection prevention committee has been weighing the evidence on all the ways in which the coronavirus spreads, including by tiny droplets or aerosols.
We acknowledge that there is emerging evidence in this field, as in all other fields, Dr. Allegranzi said. And therefore, we believe that we have to be open to this evidence and understand its implications regarding the modes of transmission and also regarding the precautions that need to be taken.
[Like the Science Times page on Facebook. | Sign up for the Science Times newsletter.]
It will also be important to understand the importance of transmission by aerosols compared with larger droplets, and the dose of the virus needed for infection from aerosols, she said.
These are fields that are really growing and for which there is evidence emerging, but it is not definitive, she said. However, the evidence needs to be gathered and interpreted, and we continue to support this.
Other experts said it has been clear for some time that airborne transmission of the virus is possible, but agreed that its not yet certain how big a role this route plays in spreading the virus.
The question of how important it is for overall transmission remains an open one, said Bill Hanage, an epidemiologist at the Harvard T.H. Chan School of Public Health.
Still, he and other experts have said that the W.H.O. is too slow and cautious in adopting precautions based on emerging evidence.
W.H.O. scientists offered an explanation for their seemingly slow pace. On average, they review 500 new papers a day, many of which turn out to be of dubious quality, said Dr. Soumya Swaminathan, the W.H.O.s chief scientist.
As such, the scientists have to review the quality of each paper before including it in their analysis, she said: Any guidance we put out has implications for billions of people around the world. It has to be carefully done.
|sars-cov-2: modes of transmission - Google Search|
|German slaughterhouse contending with COVID-19 to remain closed pending hygiene plan|
According to reporting in Reuters, the chief executive of the Guetersloh district made the announcement on 7 July.
Nearly 600,000 people in Guetersloh, a city in the western state of North Rhine-Westphalia, were forced back into lockdown on 23 June after more than 1,500 workers at the Toennies abattoir and packing plant tested positive for the novel coronavirus.
Sven-Georg Adenauer said in a news conference broadcast online that the plant could only be reopened if there is "no threat to the people who work in this company and also not to the people in the Guetersloh region".
The company had presented a hygiene plan to authorities that went in the right direction but "still needs work and I believe the company will undertake this", he said, adding it was still not possible to say when the plant would reopen.
The outbreak sparked a national debate about whether consumers should be prepared to pay more for meat to improve standards in German meat packing plants.
The plant has provisionally been ordered to close up to 17 July, Adenauer said. Health and safety officials continue to inspect it and negotiate with the company over the new hygiene plan. Another round of assessments will be made on Thursday.
Toennies did not have immediate comment. The company has previously apologised and said it is working closely with authorities on a hygiene plan to achieve a reopening.
The Guetersloh plant normally slaughters and processes between 12 percent to 14 percent of Germany's pigs and the closure is causing disruption to pig farmers, the Association of German pig farmers said.
On Monday 6 July, a court ordered an end to the lockdown in Guetersloh.
|11:27 AM 7/8/2020 - String of assassinations and attacks on Chechen exiles in Europe, Turkey and the Middle|
Russia denies charges of involvement in the wave of killings. ... MOSCOW The assassins come with pistols, hammers and knives. ... string of assassinations and attacks on Chechen exiles in Europe, Turkey and the Middle ...https://images.app.goo.gl/iXAre8V7qMhFuGEW6
11:27 AM 7/8/2020
Saved, Shared Stories, Tweets | Page | In Brief - Page | on RSS Dog In 250 Posts |
- Get link
- Other Apps
Post a Comment