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- Herausgeber: Publisher s14676
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
- Veröffentlichungsjahr: 2020
In this book are analyzed topics related to COVID-19 which form the basis of the understanding of the multiple aspects related to the protection of public health, and which will allow the reader to broaden his or her understanding of how the system of preparation for the global pandemic is developed. Today, on the eve of the first fifth of the twenty-first century, we have new tools which allow us the management of pandemics. Will be described what are those tools, deepening several topics which are interrelated and which create the healthcare system. The book focuses in particular on the management of clinical studies, the pharmaceutical patent system, gene sequencing and the role of artificial intelligence in the protection of public health and fundamental human rights, observing how all this different tools are used to address the COVID-19.
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Simone Rotili
COVID-19 LEGACY
Original title: COVID-19 LEGACY
Subtitle: SARS-CoV-2 clinical trials, vaccine trials and bioethic
All rights reserved Copyright © 2020 COVID-19 LEGACY; SARS-CoV-2 clinical trials, vaccine trials and bioethic.
No part of this book may be reproduced, copied or transmitted in any form and in any way, graphic, electronic or mechanical, including photocopies or recorded, without the written permission of the author, except where permitted by law.
Index
Preface
CHAPTER 1
What are coronavirinae
Human infections in the 21st century
Diseases caused by the coronavirinae among mammalian and aves classes
SARS-CoV-2 transmission
Phylogenetic lineage of SARS-CoV-2
SARS-CoV-2 structure and replication
The contagion
Detection and containment of the Covid-19 infection
Immediate interventions by FDA and WHO
The severity ranges of Covid-19
The psychological impact of Covid-19
Pre-existing pathologies may increase the risk of death by Covid-19
Covid-19 fatality rates and population characteristics
How the name Covid-19 has been chosen
Also animals are affected by Covid-19
The Solidarity trial on Covid-19
CHAPTER 2
Guidelines for human subject research
Early approaches to modern clinical trials: Neisser and Moll
Earliest models for human ethical experimentation until the Nuremberg Trials
The Helsinki Declaration, the Belmont Report, the Common Rule and hte FDA Code
CHAPTER 3
What are clinical trials and how do they work beyond covid-19
Brief history of the clinical trials, since 1747
Classification of clinical trials
The protocol
Some peculiar clinical trials and the CROs
CHAPTER 4
What are the phases of a clinical trial
Phase zero
"Human micro-micro dosing" to assess pharmacokinetics among several drug candidates
Phase 1 clinical trial
"First-in-humans " phase involves between 20 and 100 patients
Phase 2 clinical trial
"Proof of concept study" involves between 100-300 patients
Phase 3 clinical trial
"Pre-markegting" phase involves between 300-2000 patients
Phase 4 clinical trial
"Post-marketing" surveillance phase
CHAPTER 5
COVID-19 drugs development
Compassionate use and preclinical trials
Drug repositioning
New chemical entities
A.I. support
CHAPTER 6
An introductory look at what vaccines are
Few milestones in the history of vaccination
Several types of vaccines in use
Third generation vaccines using genetic engineering
RNA vaccines
Vaccines valency
Prerequisites to know on vaccines
Vaccination during childhood
Vaccines in animals
CHAPTER 7
What is a vaccine clinical trial
CHAPTER 8
Studies on COVID-19 vaccines
The Coalition for Epidemic Preparedness Innovations
Development stages for COVID-19 vaccines
The probability of success for a contagious disease vaccine candidate
Equity share challenges
Preparedness
CHAPTER 9
What are the ethical aspects that govern any research carried on a human being
The Institutional Review Board (IRB)
The guidelines for Good Clinical Practice
Responsibility for the safety
Primum non nocere
The scrutiny
Abroad
The aggregation of safety data
Overview of clinical trials costs and management
CHAPTER 10
Tests able to identify the coronavirinae strains
The swabs logbook
A look at immunoglobulin and PoCT
The European Approval
Scale testing up
Stay at home
The bulk assays
Testing more than any other
The call for ramping up testing
The different testing recipes
How does a swab works? The polymerase chain reaction (PCR)
The discovery of RT-PCR
How does PCR works - One step or two steps reaction
Endpoint and real-time PCR
Competitive RT-PCR and absolute quantification
Comparative RT-PCR
Four fluorescent DNA probes available for real-time RT-PCR
PCR for diagnosis of genetic diseases
The Gold Standard
Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu 1, complete genome.
The Author
Bibliography
Preface
In this book are analyzed topics related to COVID-19 which form the basis of the understanding of the multiple aspects related to the protection of public health, and which will allow the reader to broaden his or her understanding of how the system of preparation for the global pandemic is developed. Today, on the eve of the first fifth of the twenty-first century, we have new tools which allow us the management of pandemics. Will be described what are those tools, deepening several topics which are interrelated and which create the healthcare system. The book focuses in particular on the management of clinical studies, the pharmaceutical patent system, gene sequencing and the role of artificial intelligence in the protection of public health and fundamental human rights, observing how all this different tools are used to address the COVID-19.
CHAPTER 1
What are coronavirinae
Coronaviruses were first discovered in the 1930s, when acute respiratory infection among chickens was shown to be caused by the contagious bronchitis virus. In 1931 a new respiratory infection of chickens in North Dakota was described by A. Schalk and M. Hawn. Chick infection was characterized by laziness and prostration. The mortality rate of the chicks was 60%. In 1938 the contagious bronchitis virus was successfully isolated from F. Beaudette and C. Hudson. In the 1940s, two additional animal coronavirinae strains were isolated: the mouse hepatitis virus and the transmissible gastroenteritis virus. At that time there was no awareness of the relationships between the three viruses. We come to the discovery of human coronavirinae strains only 20 years later in the 1960s. A new cold virus called B814 was isolated in 1960 from the Common Cold Unit of the British Medical Research Council by E.C. Kendall, Malcom Byone and David Tyrrell. The virus did not seem to be easily cultivated using the common cultivation vial which, on the contrary, had been successfully used to grow rhinovirus, adenovirus and other cold viruses. Five years later, Tyrrell and Byone successfully cultivated the new virus by serially introducing strains within the cultures of the human-derived embryonic trachea. The same year at the University of Chicago a new cold virus, later called 229E by medical students, was isolated from professors D. Hamre and J. Procknow, who used a different cultural approach to grow the virus in culture. kidney tissue. The new 229E virus, such as the viral strain B814, when inoculated in volunteers caused a cold and was inactivated by the ether, indicating that both viruses had a lipid envelope. Most viruses such as HIV have the so-called viral envelope as an outer layer in their life cycle stage when they live outside the host. This happens because the envelopes are generally derived from portions of the membranes of the host cells (phospholipids and proteins), but also include some viral glycoproteins and not only those of the host. They may prefer viruses to avoid the host immune system. The glycoproteins found on the surface of the envelope are useful for identification and binding with receptor sites on the host membrane. The viral envelope eventually merges with the host membrane, which allows the capsid and viral genome to break through and infect the host. Varieties B814 and 229E were officially photographed for the first time by an electron microscope by J. Almeida, a microbiologist who worked for St Thomas Hospital in London. Thanks to electron microscopy, Dr. Almeida was able to highlight that both strains could be distinguished from the peaks like those of a club. Thanks to Dr. Almeida not only was it possible to understand the morphological relationship of the two strains that were very similar to the contagious bronchitis virus. Following the National Institute of Health of the United States of America he was able to detect another virus called OC42 which belongs to the same family. The NIH isolated the virus and was able to allow the scientific community to study these viruses and their relationships, and the conclusions thanks to the electron microscope in which these viruses had distinctive peaks similar to those of a club, each of which has its own strain. Coronaviridae are a group of viruses that can cause disease in mammals and avian species. These viruses are the causative agent of respiratory tract infections which, due to our misunderstanding of the mechanism of action, can vary from mild to lethal. In describing mild disease, they include colds, keeping in mind that they are not the only family of viruses that cause colds, which are mainly caused by the rhinovirus family. The lethal strains of coronaviridae have been found to be the causative agents of severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS) and coronavirinae strain 19 disease (covid-19). For all these viral diseases there is a wide range of symptoms that affect not only humans but also other mammals and avian species, as we have just anticipated above. We can observe that in chickens, these viruses cause a respiratory tract infection differently from pigs in which the same strain mainly causes diarrhea. Since 2002 there have been numerous patents on vaccines and antivirals of coronaviridae, but unfortunately it has not been possible to prevent this disease, to spread further for various reasons related both to the mutagenicity of this family of viruses, and to the patent system that must guarantee the confidentiality of data in order to protect researchers' rights and for the practical construction of the laboratories needed to produce an antiviral drug or vaccine in time.
According to the International Committee for the Taxonomy of Viruses, the strains of coronavirinae are a subfamily of the ortho-coronavirinae, which belong to the wider family of coronaviridae, which are grouped in the order of nidovirales, which are further collected in the kingdom of riboviria (which collects all ribonucleic acid viruses). According to the Baltimore classification, coronavirinae strains are viruses wrapped with a positive-sense single-strand RNA (+ssRNA) gene pool. The genome size of the coronavirinae strains is between 26 and 32 kilobases (one kilobase - "kb" - means 1000 nitrogen bases), i.e. it extends from 26,000 to 32,000 nitrogen bases. The nitrogen bases that make up nucleic acids in biochemistry are one of the four components of organic life together with sugars, lipids and proteins. They have characteristic club-shaped tips that protrude from their surface, which in electronic micrographs create an image that resembles the solar crown, from which their name derives. Coronavirinae are spherical stones with spike-like protrusions that have a size of almost 17-22 nm, which make up the proteins encoded by its genome, the average diameter of these spheres is 80 nm (1 nano-meter - "nm "- It's one billionth of a meter, or 1 meter divided 1,000,000,000 times). To be even more correct, we must add that obviously they do not all have the same dimensions; but the size varies from 60 nm to 120 nm. To be even more precise on the size, we can consider the fact that the diameter of the envelope varies within 80 nm while the diameter of the tips, as we have just said, varies within 20 nm for this reason, we will estimate the dimensions based on the fact that we consider the peaks or if we start measuring from the internal spherical diameter. The envelope consists of a double-layer lipid membrane derived from the host during bubbling. Inside the envelope, there is the nucleocapsid, which is made up of copies of the nucleocapsid protein and those are linked to the + ssRNA of the coronavirinae. The lipid bilayer envelope and the nucleocapsid together perform the function of protecting the virus outside a host. The coronavirinae replication cycle is divided into four main phases: entry, replication, release and transmission. Contagion begins when glycoprotein (the peaks) attaches to its complementary host cell receptor. Declaring protection of the host cell divides and activates the receptor. The cleavage and activation set the entry of the virus into the host cell via a mechanism known as endocytosis (on some microbiology textbooks also called "direct fusion") of the viral envelope with the host membrane. After entering the host cell, the viral chapter is more widespread, as it is uncoated and its genome floats within the cell cytoplasm. The coronavirinae genome + ssRNA has a 5 'methylated cap (containing several methyl groups); and a 3 'polyadenylated tail (also known as poly-A, containing almost 200 nitrogen bases supplied only adenine), this is necessary for the RNA to adhere to the host cell ribosome and translation begins. The host's ribosome translates the genome into a long polyprotein. This polyprotein contains its own proteases which subdivide the integrated polyprotein into several unintegrated proteins. When several unstructured proteins are formed, they aggregate to form a multiple complex of replicated-transcriptase proteins (also known as RTC - that is, replicase transcriptase complex). At this point, since the main replicase-transcriptase protein is RNA-dependent RNA polymerase (also known as RdRp), it begins to replicate and transcribe RNA from an RNA strand. The remaining unstructured proteins are believed to aid in replication and transcription, but not all functions of unsecured proteins are known to give just one example, exo-ribo-nuclease proteins, responsibilities to support replication by increasing the proofreading function of RdRp. Viral genome. RdRp media selected the synthesis of negative sense RNA from positive sense RNA followed by replication of positive sense RNA from negative sense RNA. Another important function of the complex is the transcription of the genome of the virus itself, and this process is also mediated by RdRp through the synthesis of RNA molecules of negative sense from RNA of positive sense, followed by the transcription of this story the molecules of RNA in their correspondent messenger RNA. What has just been replicated, which is the positive sense RNA at this stage, becomes the genome of future viruses, the "sons and daughters" of the virus. The negative-sense RNA. Another important function of the complex is the transcription of the genome of the virus itself, and also this process is mediated by RdRp through the synthesis of negative-sense RNA molecules from the positive-sense RNA, directly followed by the transcription of such negative-sense RNA molecules into their corresponding messenger RNA. What has just been replicated that is the positive-sense RNA at this stage becomes the genome of the future viruses the “sons and daughters” of the virus. Messenger RNAs are transcripts of the last third of the viral sequence from the initial reading frame. This messenger RNA is translated by ribosomes within the eukaryotic cell into proteins that will form the structure of the virus plus other functional proteins whose activity has yet to be fully understood. The above process occurs within the endoplasmic reticulum of eukaryotic cells in which the structural proteins of the virus continue through the secretion pathway inside the Golgi apparatus where they find the machine necessary for assembling new viruses and from the exocytosis these new carriers are finally released outside the cell. In conclusion of the replication cycle, the coronavirinae interaction of the peak protein with the receptor of the complement host cell is central in determining the tropism of the tissues, but also the infectivity.
Human infections in the 21st century
Coronavirinae has a wide range of variations considering the risk factor. There are strains that have reached a killing rate of 30% of infected mammals, such as MERS-CoV, while other strains are relatively harmless or completely harmless. Coronavirinae as many of you as readers already know from the news or as a personal experience if you have been infected with the coronavirinae strain and have suffered the symptoms, knows the maximum common symptomatology caused by the infection of the coronavirinae strain, which can extend from cold main symptoms, such as fever, sore throat, swollen throat, swollen adenoids dry cough, dyspnea, diarrhea etc. Coronavirinae can also cause pneumonia or bronchitis directly or indirectly. Seventeen years ago, in 2003, another coronavirinae strain, SARS-CoV, infected humans, was the causative agent of severe acute respiratory syndrome (SARS) and had the particularity of infecting both respiratory tract infections higher than lower, as is happening with SARS-Cov-2, which is the pathogen of Coronavirus 2019 (covid-19). In nature there are seven known strains of coronavirinae that can infect humans, among these four are the cause of the cold every year, the OC43 strain, the HKU1 strain, which are two beta coronaviridae; and the variety 229E and the variety NL63, which are alpha-coronaviridae. It is important to emphasize when speaking of alpha and beta coronaviridae that coronavirinae infect both animals and humans. While alpha and beta are derived from the bat gene pool, the gamma and delta genera are derived from the bird and pig gene pool. Among the seven coronavirinae known to infect three humans they can cause more severe symptoms, and those are the SARS-CoV strain, the MERS-CoV strain and the SARS-CoV-2 strain, all of which are coronaviridae beta. In 2002-2003, after the outbreak of severe acute respiratory syndrome (SARS), the World Health Organization (World Health Organization) released a press release warning that a new coronavirinae strain had been identified by a number of laboratories and who appeared to be the causative agent for SARS. The virus has been officially called the SARS coronavirinae (SARS-CoV) strain. In the 2012-2013 period, a new strain of coronavirinae was identified, and after several names where it was suggested that it was finally officially called the Middle East Respiratory Syndrome (MERS-CoV). Again, the World Health Organization has warned the world of the global alert. The World Health Organization, on September 28, 2012, stated that the virus does not seem to spread easily among the population. However, on May 12, 2013, a human transmission case in France was confirmed by the French Ministry of Health. In addition, cases of human-to-human transmission have been reported by the Ministry of Health in Tunisia. Two confirmed cases involved people who appeared to have contracted the disease from their father, who fell ill after a visit to Qatar and Saudi Arabia. Despite this, it appears that the virus had difficulty in spreading from man to man, since most of the infected people did not transmit the virus. The Dutch Erasmus Medical Center has sequenced a variety of coronavirinae which have been given a new name, Human Coronavirus - Erasmus Medical Center (HCoV-EMC). In 2015, a MERS-CoV outbreak also erupted in the Republic of Korea, when a man who had traveled to the Middle East visited four hospitals in the Seoul area to treat his illness. This caused one of the biggest MERS-CoV outbreaks outside the Middle East. By December 2019, 2,468 cases of MERS-CoV infection had been confirmed by laboratory tests, 851 of which were fatal, a mortality rate of around 34.5%. In December 2019, a pneumonia outbreak was reported in Wuhan, China. On December 31, 2019, the outbreak was traced to a new variety of coronavirinae, which received the tentative name 2019-nCoV from the World Health Organization (World Health Organization), later renamed SARS-CoV-2 by the Committee. International for Taxonomy of Viruses (ICTV). As of April 27, 2020, there have been at least 206,569 confirmed deaths and over 2,973,264 confirmed cases. The Wuhan strain has been identified as a new beta-coronavirinae strain with approximately 70% genetic similarity to SARS-CoV. The virus has a 96% similarity to a bat coronavirinae strain. The pandemic resulted in travel restrictions and national blockades in several countries. Coronaviruses have been recognized as the cause of pathological conditions in veterinary medicine since the 1930s.
Diseases caused by the coronavirinae among mammalian and aves classes
Coronavirinae mainly infect the upper respiratory tract of mammals and birds. They also cause a range of diseases in farm animals and pets, some of which can be serious and are considered a threat to the agricultural sector. In chickens, for example, the contagious bronchitis virus (IBV), which as we discussed in chapter 1 belongs to the coronavirinae, affects not only the respiratory tract but also the urogenital tract. This virus can spread to different organs around the chicken. Before the discovery of SARS-CoV, the mouse hepatitis virus (MHV) was the most studied coronavirinae strain both in vivo and in vitro. Some strains of MHV cause progressive demyelinating encephalitis in mice which has been used as a mouse model for multiple sclerosis. Significant research has aimed to clarify the viral etiopathogenesis of these mammalian coronavirinae, by experts in veterinary and zoonotic diseases. Concerning extremely economically relevant farm animals, including bovine coronavirinae strains and porcine coronavirinae strain which causes the coronavirinae strain of transmissible gastroenteritis, both of which cause diarrhea in young animals. Pathologically, feline coronavirinae strains are present in two forms, the feline enteric coronavirinae strain is a less relevant clinical pathogen, even though spontaneous mutation of the coronavirinae strain usually causes contagious feline peritonitis. (also called FIP by veterinarians), which has a high mortality rate among the felid family. There are two strains of coronavirus strain that infect ferrets and also cause a gastrointestinal syndrome known as catarrhal epizootic enteritis (classified as ECE by veterinary surgeons) and an even more lethal systemic version of the virus known as the systemic coronavirinae strain of ferret (classified as FSC by veterinarians). In addition, continuing with chips there are two types of canine coronavirinae strains (so-called CCoV by experts), one of which causes gastrointestinal disease and another which has been found to cause respiratory disease. The mouse hepatitis virus (known as MHV) is a coronavirinae strain with the ability of an epidemic murine disease with high mortality, especially among colonies of laboratory mice. The sialo-dacryoadenitis virus (SDAV) is a highly contagious coronavirinae strain of laboratory rats in which acute infections have a high morbidity for the salivary, lacrimal and harderian glands and which can be transmitted between people both by direct contact and indirectly through aerosol. Just to allow a broader view of the coronavirinae pat strains currently known we can mention a few such as the enteric rabbit strain coronavirinae which causes acute gastrointestinal disease and diarrhea; the porcine coronavirinae strain (transmissible strain of porcine gastroenteritis coronavirinae, also known by veterinarians as TGEV); the swine epidemic diarrhea virus (also called PED); the turkey coronavirinae strain (known among veterinarians as TCV) causes enteritis in turkeys; the bovine coronavirinae strain (also known by veterinary doctors as BCV), responsible for severe profuse enteritis; the contagious bronchitis virus which is the cause of avian contagious bronchitis (also known by the veterinary surgeon as AIB); the feline strain of coronavirinae which is the cause of enteritis in cats (as we have already said) and severe feline contagious peritonitis; the ferric strain coronavirinae ferret (also mentioned above) and the ferric strain coronavirinae ferret causes epizootic catarrhal enteritis in ferrets; the two types of canine coronavirinae strain (again mentioned above) one of which causes enteritis, the other causes respiratory disease and the canine pantropic coronavirinae strain.
SARS-CoV-2 transmission
Acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2) is the viral strain that causes coronavirinae strain disease 2019 (covid-19), also in animals. It is known as the coronavirinae variety worldwide although more appropriately we should refer to it using its viral code or as a variety of coronavirinae, and previously it was referred to by its tentative name 2019 new variety of coronavirinae ( 2019-nCoV According to ICTV SARS -CoV-2 is a serious strain of coronavirinae strain related to acute respiratory syndrome (SARSr-CoV). It is thought to have zoonotic origins and has a close genetic similarity to bat strains, suggesting that it emerged from a bat strain. also be connected to an intermediate animal tank in pangolins, for its transmission. The virus shows genetic diversity, indicating that the spillover event introducing SARS-CoV-2 to humans has probably occurred at the end of 2019. SARS-CoV-2 previously anticipated in this chapter is a positive-sense single-stranded RNA virus (+ ssRNA according to the classification of Baltimore). The World Health Organization has designated the ongoing pandemic of covid-1 9 as an infection contagious to both animals and humans.
Numerous epidemiology studies evaluate the results of each infection in 1.4 - 3.9 new infections when any member of the community is immune and preventive measures are not taken. The virus initially spreads through people through contacts and closeness and mainly through respiratory droplets produced by breathing, coughing or sneezing. It mainly enters human cells through the angiotensin receptor by converting the boundary of the enzyme 2.
Transmission between humans of SARS-CoV-2 was confirmed on January 20, 2020, during the coronavirinae strain pandemic 2019-2020. This transmission occurs primarily through coughing and sneezing respiratory droplets within a radius of about 6 feet. It could be caused by contaminated fomites, which are another possible cause of the infection. Previous research indicates that this viral family can remain viable on smooth surfaces and iron for up to three days, but does not survive on cardboard for more than one day or on copper for more than four hours; coronavirinae are easily washed with soap, clinging to their lipid double layer. In the earliest stages of the contagion that occurred in China, in Wuhan city, the virus and disease were called "Wuhan coronavirinae strain" or "Wuhan virus" in accordance with the historic naming conventions that give the name to a new pathogen of consequence to the city or region of the world in which it first appeared. However, the World Health Organization has suggested actions against the use of positions in disease and virus names since 2015, and for this reason the World Health Organization has not included "Wuhan" in the official name and has discouraged such use. of the name of the disease. In order to encourage research and communication processes around the world, the World Health Organization has in the early stages of the infection the name of the virus with a temporary name "2019 novel coronavirinae strain" (2019-nCoV). On February 11, 2020, the World Health Organization renamed it giving the official name of "acute respiratory strain coronavirinae syndrome 2" (SARS-CoV-2). In order to avoid misunderstandings with SARS, the diseases have been called covid-19 "caused by the" covid-19 virus "which is also acceptable in public health communications. The United States government and President Donald Trump have called it "the Chinese virus" or "the Chinese virus" using the orthodox nomenclature as has been done for the most relevant pandemics in human history. Some people may consider these terms racially accused and some claim that they contribute to racism, but this only has geographical reasons.
Phylogenetic lineage of SARS-CoV-2
The level at which the virus is contagious during the incubation period is not always the same for everyone, but research has pointed out that the pharynx peaks viral load about four days after infection or the first week of disease manifestation. and decreases after that period. On February 1, 2020, the World Health Organization demonstrated that "transmission from asymptomatic patients is not an important transmission factor". However, an epidemiological model established from the earliest stages of the disease in China has shown that "pre-symptomatic signs may be characteristic in documented infections" and clinical contagion may be the cause of a large majority of infections. A study involving 94 hospitalized patients in January and February 2020 spilled the largest number of viruses two to three days before any symptoms appeared and for this reason some transmission interval may occur before the initial symptoms in the index case. There is also evidence of human-animal transmission of SARS-CoV-2, including examples in cats. several authorities have warned people infected with SARS-CoV-2 to limit contact with their taps.
Given that a huge amount of initial individuals found infected with coronavirinae were workers in the Huanan fish market, it was suggested that the strain could have gone out of the market; but further research shows that many market guests may have introduced the virus to the market as well, which may have facilitated a rapid outbreak of the infection. A phylogenetic analysis of the network of 160 first genomes of the coronavirinae strain sampled from December 2019 to February 2020 revealed that the coronavirinae strain closely related to the bat strain was mainly abundant in the Guangdong region of China, and designated the type as type A. The predominant type among the samples from Wuhan was identified as B which was not related to the bat coronavirinae strain compared to the ancestral type A.
The deepening of the natural reservoir of the coronavirinae strain that caused the SARS epidemic of 2003 led to the discovery of many bat coronavirinae related to SARS, most of which originate from the Rhinolophus genus of horseshoe bats. Further phylogenetic investigations show that samples taken from Rhinolophus sinicus show an 80% similarity with SARS-CoV-2. However, the phylogenetic analysis indicates that a Rhinolophus affinis virus, collected in the province of Yunnan and designated RaTG13, has a 96% similarity with SARS-CoV-2, while the coronavirinae strain of pangolin has a 92% similarity with SARS -CoV-2.
At first, bats were thought to be the natural reservoir of SARS-CoV-2, but the differences between the bat coronavirinae sampled at the time and SARS-CoV-2 showed that humans were infected with an intermediate host. A study conducted by Arinjay Banerjee at McMaster University shows that the SARS virus shared 99.8% of its genome with a civet coronavirinae strain, which is why civets were considered the source. In addition to the fact that the searches had guessed some potential candidates, the number and identities of the intermediate hosts is still ambiguous. Almost 50% of the strain genome had a phylogenetic lineage distinct from known coronavirinae.
A genomic study published in 2019 before the epidemic shows that SARS-CoV, the causative agent of SARS, was the most widely distributed coronavirinae strain within a sample of pangolins. On February 7, 2020, Guangzhou South China Agricultural University announced that researchers had discovered a sample of pangolin with a single viral RNA sequence "like 99% that of a SARS-CoV-2. From this research it emerged that the receptor - the binding domain of the newly discovered pangolin coronavirinae strain protein is identical to that of 2019-nCoV, with single polymorphism; for this reason this protein, or spiked protein, of the coronavirinae strain binds to the cell surface receptor during infection, they are protected animals in China, but their poaching and trade for use in traditional Chinese medicine is still widespread.
Phylogenetic investigations indicate that pangolins could be a host reservoir of coronavirinae like SARS-CoV-2. Yet there is no evidence to connect pangolins as an intermediate SARS-CoV-2 host at this stage. While there are several scientists who agree that bats are the final source of coronavirinae, similar strains of coronavirinae, very similar to SARS-CoV-2, are believed to have originated in pangolins, transmitted to bats and then transmitted to the bats. man, resulting in SARS-CoV-2. Based on the entire similarity of the genomic sequence, it was found that a very similar pangolin strain candidate coronavirinae is like SARS-CoV-2 but is more similar than other coronavirinae to SARS-CoV-2. Consequently, based on maximum frugality, a designated population of bats is more likely to have infected a human directly with SARS-CoV-2 than a pangolin, while an evolutionary ancestor of bats was the source of the general strain of coronavirinae. Despite previous findings, Texas immunologists have conducted personalized research showing evidence of reassortment in coronavirinae suggesting the involvement of pangolins in the origin of SARS-CoV-2. SARS-CoV-2, as we have said, belongs to the broader family of viruses known as coronaviridae. Other coronavirus can cause diseases ranging from the common cold to more serious diseases such as Middle East MERS respiratory syndrome. Like the SARS-related strain of coronavirinae involved in the SARS epidemic 2002-2004, SARS-CoV-2 is a member of the Arenavirus β-CoV B lineage. Its RNA sequence, as we discussed above in this chapter, is approximately between 26,000 and 30,000 bases in length. SARS-CoV-2 is unique among the well-known β-coronavirinae in its integration of the cleavage site, which is a characteristic known to improve the pathogenicity and the spread to other viruses.
