مقالات پذیرفته شده در پنجمین کنگره بین المللی زیست پزشکی
Phylogenetics, molecular biology and clinical aspects of corona virus
Phylogenetics, molecular biology and clinical aspects of corona virus
Negin Motavalizadehkakhky,1,*Hadith Nasrabadi,2Zahra Kheiri,3Mahshid Meshkani,4Negar Motavalizadehkakhky,5
1. Mohebbi Model School, 10th grade, Neyshabur, Iran 2. Mohebbi Model School, 10th grade, Neyshabur, Iran 3. Mohebbi Model School, Neyshabur, Iran 4. Islamic Azad University, Neyshabur Branch, Neyshabur, Iran 5. Islamic Azad University, Faculty of Pharmacy, Damghan Branch, Damghan, Iran
Introduction: Abstract:
Background and Purpose: COVID-19 is a viral respiratory illness. In this paper, we take a look at the Coronavirus genome, the symptoms of coronavirus (COVID-19), coronavirus prevention and treatment as well as different types of COVID-19 vaccines.
Materials and methods: the articles were searched looking for keywords including COVID-19, vaccine, treatment, prevention, and genomic structure of the virus. It is worth mentioning that reliable websites and other references are used to obtain information about developing a novel vaccine have been listed and referenced at the end of the article.
Results: In late 2019, a new viral disease broke out in China which was named COVID-19 by WHO. Due to the similarity to the virus causing acute respiratory syndrome and SARS virus, it was called Sars-CoV-2. This virus causes a life-threatening lower respiratory tract infection1.
Methods: Materials and methods: the articles were searched looking for keywords including COVID-19, vaccine, treatment, prevention, and genomic structure of the virus. It is worth mentioning that reliable websites and other references are used to obtain information about developing a novel vaccine have been listed and referenced at the end of the article.
Results: Results: In late 2019, a new viral disease broke out in China which was named COVID-19 by WHO. Due to the similarity to the virus causing acute respiratory syndrome and SARS virus, it was called Sars-CoV-2. This virus causes a life-threatening lower respiratory tract infection1.
Conclusion: Conclusion:
Coronavirus causes COVID-19 viral disease, affecting a large number of people around the world. In general, virus entry to the host cells is mediated by spike protein (crown-like proteins) and hence it can be taken into account as an appropriate candidate for efficient vaccine design. This protein enters the host cells through human ACE 2 receptors. This receptor has been detected in some organs including the lungs, heart, liver, kidneys, brain, and bladder, and hence these organs can be severely damaged due to COVID-19 infection6. Antigen-specific antibodies are secreted in response to the coronavirus attack and consequently, the body is protected against virus reattack.
Coronavirus mutations do not happen quickly and the virus genome mutates in terms of changes in the amino acid structures. This change may occur due to nucleotide addition or deletion from the viral genome. To prevent the disease before applying an efficient vaccine, people should follow the recommended instructions and observe personal proper hygiene to keep themselves, their families, and their community healthy and visit a doctor in the presence of any symptoms or clinical manifestations.
Investigations on the efficiency of various available vaccines reveal that the killed viruses in a vaccine function more efficiently compared with a membrane protein. Because the membrane protein should be combined with a non-pathogenic virus like adenovirus-based vectors and this virus may be deactivated by the human body immune system and consequently, its efficiency decreases.
Innovation:
Coronavirus can introduce to the human body through one of the viruses which people are vaccinated against it in childhood, so it can stimulate immune system response and consequently releasing coronavirus antigen-specific antibodies. This sequence of events leads to virus destruction and prevents COVID-19 development. Surveys demonstrate that compared with using viral proteins, using killed viruses provide more effective immunity, as they are resistant to all mutations. We hold this view that applying combination of the killed virus vaccine like smallpox (because smallpox is a viral disease which can be transmitted through cows to humans as an intermediate host, while cows themselves are not affected by the virus and our immune system knows the smallpox virus from our childhood because we have vaccinated for smallpox virus) with killed coronavirus (a new virus for our immune system) is more efficiently in comparison with other types of available vaccines. It can be explained that since there is an immunologic memory against smallpox in the human body, the immune system initially identifies smallpox and then the coronavirus genome within. After that, specific antibodies against the smallpox virus are released and then there is a high possibility of trapping the virus compared with using other viruses. This approach has a lot of advantages. For instance, in the USA, in nursing homes, where the elderly received Pfizer vaccine, several deaths were reported. It can be explained by this fact that the immune system of these people is not strong enough to fight against the virus and are weaker compared with the other age groups of people. These deaths may have happened due to the formation of a blood clot. So, by taking the advantage of this approach, we provide a guide for white cells to fight against the virus rapidly and maybe prevent clot formation in the elderly people.
It is recommended to receive medication in the second and third phases through nasal injection because COVID-19 is a respiratory disease and macrophages inside the lungs as phagocytes can destroy the virus easily and prevent developing respiratory disease.
It should be noted that sometimes this approach does not work. However, even if this theory is rejected, these viruses can still stimulate antibody production and develop resistance to the virus but how? That is the question. Firstly, a new virus may develop which cannot be recognized by the human immune system, so there is no memory. Yes, that is possible. However, this vaccine contains killed viruses so it is safe and harmless. Secondly, the human body produces antibodies even against these viruses and it will has a function like previously developed vaccines like sputnik V and stimulate immunity in the human body.
Introduction:
In late 2019, a case of pneumonia of unknown etiology was reported in Wuhan City. This pneumonia caused symptoms including dry cough, fever, shortness of breath, and acute respiratory syndrome. The clinical symptoms of patients were similar to phylogenic of the coronavirus and therefore, WHO named it COVID-19.
This virus belongs to the Betacoronavirus family (HCOV-OC43, HCoV-MERS) 2, and like its other relatives, is capable of infecting a wide variety of organisms serving as intermediate or final hosts. The genome sequence of coronavirus is 88% similar to the two Betacoronavirus types of acute respiratory syndrome-like diseases and 50% similar to the genomic sequence of Mers-CoV. Genomic analysis of this virus reveales the homology with bat coronaviruses or SARS genomes, implying the possibility of COVID-19 transmission from bat to human.
This article elucidates biology, genomic structure, ways of transmission, the symptoms of coronavirus infection, prevention, and treatment, comparison of available vaccines, and eventually the mechanism underlying the action.
Coronavirus biology: coronavirus is referred to as a group of viruses. The term "Corona" means crown which refers to the appearance of the virus under a microscope. This virus has a fringe of large, bulbous surface projections and looks like a royal crown3.
Coronaviruses are a large family and give rise to asymptomatic common colds. They affect the lungs and cause acute respiratory diseases like SARS. In February 2020, the International Committee on Taxonomy of Viruses (ICTV) called it Severe Acute Respiratory Syndrome Type 2. Over the past two decades, corona caused three acute respiratory epidemics namely null corona, severe acute respiratory syndrome (SARS), and Middle East Respiratory Syndrome (MERS)1. The members of the corona family have capsids and their genetic material is a single-stranded positive ribonucleotide4. On the capsid, there are glycoprotein structures called spikes (rod-shaped)1. Other protein compounds are also found on the capsid and protein envelope of coronaviruses' genetic material. The type and structure of these compounds stimulate human immune system response, and that is why they are called viral antigens5.
Angiotensin-converting enzyme 2 (ACE2) receptors mediate Severe Acute Respiratory Syndrome Type 2 entrance to the host cells. Virus binding to ACE 2 receptors plays a crucial role in infecting human lung cells and associated pathogenicity6. This virus has presumably originated from bats and has been adapted to infect human cells. Virus directly enters host cells through membrane fusion and then endocytosis. After that, genetic material is released into the cytoplasm. Initially, glycoprotein components of the capsids are made and these components enter to the Golgi apparatus and endoplasmic reticulum. Released by budding as small vesicles from the intracellular membranes, new mature virus particles are fused with the host cell membrane, and finally, surrounded by host cell-derived lipid membranes are released1,7.
Coronavirus genome: As an RNA virus, the Corona genome consists of a helical or circular nucleocapsid. This virus codes replicase as an enzyme that consequently produces new transcripts. As the virus enters host cells, the viral genome is replicated and the virus starts amplification. Sometimes, an error occurs that changes the RNA sequence. These changes are known as mutations8.
Coronaviruses are genetically divided into 4 groups including alpha, beta, gamma, and delta. Alpha and beta infect mammalians, while gamma and delta infect birds. SARS and MERS are highly pathogenic and are transmitted to humans through Civet and camel respectively. Coronavirus genome size ranges from 26000 to 32000 base pairs and can have a varied number of open reading frames between 6 and 11. 67% of ORFs code non-structural proteins and 33% code structural and helper proteins. The structural glycoproteins include: A) spike protein (S) B) small envelope protein (E) C) matrix protein (M) and D) nucleocapsid protein (N)2.
The symptoms of coronavirus (COVID-19): the most common symptoms of coronavirus are as follows: cough, tiredness, fever, runny nose or nasal congestion, headache, gastrointestinal symptoms like nausea and vomiting, loss of sense of smell or taste. Moreover, in severe cases respiratory problems, shortness of breath, lung infection and kidney failure are also observed. The associated symptoms are divided into 4 groups: a) asymptomatic b) the onset of symptoms: fever lower than 38 °C, sore throat without nonproductive cough, smell or taste loss, nausea, vomiting, anorexia, diarrhea, muscle aches, and tiredness c) stage 2 (respiratory stage): intermediate: more severe symptoms, gastrointestinal and neurological symptoms, shortness of breath, feeling of pressure and pain on the chest with no fever. In the second stage, the involvement of three or four pulmonary lobes at most with an area involvement of less than one-third of each lobe or one or two lobes with a larger area is also observed. D) Severe: affecting over 50 percent of the lungs.
Laboratory findings: elevated liver enzymes or triglycerides, organ failure, increased or decreased platelets, slightly elevated troponin levels, and low eosinophil count2.
Coronavirus prevention:
Wearing face masks by patients and others, frequent hand washing, avoiding close contact with patients, etc. is highly recommended2.
Different types of COVID-19 vaccines:
1. Initially developed in Russia, Sputnik V was the first vaccine produced against coronavirus worldwide. In this vaccine, coronavirus along with two other manipulated types enter the host cells. The vaccine makes the host cells copy the horny protein of the virus to stimulate the immune system to produce antigen-specific antibodies against wild-type viruses9, 10.
2. Non- replicating vectors vaccines including Oxford/AstraZeneca vaccine (Sweden-England), Gamaleya (Russia), and Johnson & Johnson (the USA). In this vaccine, a segment of the viral genome that codes for viral spike antigen is selected. This segment is changed so that spike protein is fixed on the cell surface. Gene expression is regulated by a designed specific promoter. This segment is inserted into a harmless carrier (vector) like adenoviruses which are unable to replicate6.
3. Vaccines contain Killed pathogens such as shafapharmed (Iran) and Sinopharm (China): in this type of vaccine, viruses are firstly cultured in standard cells and then deactivate by chemicals such as β-Propiolactone or gamma radiation so that their structure is preserved. Compared with the vectors, they are easier to produce, have a longer shelf life, have higher stability if kept refrigerated, do not replicate in the body, and last but not least, stimulate to produce good neutralizing antibodies6, 11-13.