Jawaher Zaid Almarri Ja1909319 L52 Strategies to fight the Novel Coronavirus SARS-CoV2 Background: The structure of SARS-CoV-2 determined from the genome information of the virus. 2 3 SARS-CoV-2 is a positive single-stranded (+ssRNA) RNA virus, and RNA itself, the viral genome, acts as a transcript. This gene encodes a number of structural proteins including the four major proteins: Spike(S) glycoprotein, Nucleoprotein(N) protein, Membrane(M) protein, and Envelope(E) protein. S protein is a protein located in the outer shell of the corona virus and is involved in the penetration of the virus into the host cell through interaction with the host cell's receptor. Protein N binds to the viral RNA to form the nucleocapsid, a type of protein shell that protects the viral genome. In addition, it is an important protein that plays a role in stabilizing and packaging the genome in virus particle assembly, envelope formation, and RNA synthesis. Protein M plays a role of connecting this capsid and membrane (phospholipid bilayer, a kind of membrane), and finally, protein E is involved in the assembly and ejection of viruses and constitutes the outer shell. Pathogenesis: Pathogenesis: Studies show that multi-organ infection of SARS-CoV-2 can occur through the angiotensin-converting enzyme 2 (ACE2) receptor, which is found almost everywhere in the body. Located on the surface of many immune and non-immune cells, ACE2 is an enzyme that belongs to the system that regulates blood pressure, fluid and electrolyte balance. It is also involved in regulating the cardiovascular system, the nervous system, kidney function, and fertility. How does SARS infect humans? Coronavirus, as its name suggests, is an important weapon for infecting people with spike proteins that protrude like a crown from the outside. ACE2, a cousin of angiotensin-converting enzyme (ACE), is said to play a role in SARS-CoV-2 receptors. Currently, SARS-CoV-2, the younger brother of SARS, the nightmare of the whole world, is known to use the same ACE2 receptors to invade our bodies. By drawing an easy-to-understand picture, a receptor protein, which locks in our body called ACE2, opens the door to human cells by inserting a key called Spike Protein for Coronavirus. The better the spike key binds to ACE2 lock, the more open the human infiltration pathway, the greater the possibility of infection, and ACE2 is known before ACE2, which acts as an invasion channel for Coronavirus. The angiotensin-converting enzyme, acting on angiotensin and bradykinin, to narrow the blood vessels and cause hypertension ..; ACE2 has a similarity of 42% with the ACE mineral catalytic domain. In addition to converting angiotensin 2 (Ang II) to Angiotensin Ang- (1-7), ACE2 and physiological or pathological changes are involved in the generation of Angiotensin and Ang(1-7). However, in ACE and ACE2, proteases degrade the peptides. They are found in different locations and have different substrate properties. Strategy to stop SARS-CoV 2: SARS-CoV-2 infection can be prevented in humans using ACE2 inhibition by demonstrating its ability to fight viruses by synthesizing human proteins associated with coronaviruses. By linking the coronavirus to the water-soluble ACE2 protein that was placed in place of ACE2 in the host cell. The war between humans and viruses is hidden. Coronavirus uses the ACE2 protein, which plays a role in preventing lung damage in our bodies, as an invasion passage into the lungs. This therapeutic filter causes the introduced virus to recognize and bind recombinant ACE2 as a true receptor. Viruses that bind to the fake receptors die naturally. These protein fragments, called "nsp-nonstructural proteins," also cause the virus to replicate in host cells. Non-structural proteins, such as Lego blocks, must be split into 16 pieces to perform each task. Therefore, inhibiting this mitosis process also limits virus growth. For example, Kaletra (a mixture of lopinavir and ritonavir) was developed as a proteinase inhibitor of HIV. Kaletra is undergoing clinical trials as a candidate for treatment of SAV-2, but it is not easy to expect a significant therapeutic effect from the reports so far. Jawaher Zaid Almarri Ja1909319 L52 - References: 1. Chen N, Zhou M, Dong X et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 395(10223), 507–513 (2020).Crossref, Medline, CAS, Google Scholar 2. Jia HP, Look DC, Shi L et al. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. J. Virol. 79(23), 14614–14621 (2005).Crossref, Medline, CAS, Google Scholar 3. Xu H, Zhong L, Deng J et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int. J. Oral Sci. 12(1), 8 (2020).Crossref, Medline, CAS, Google Scholar 4. Jia HP, Look DC, Shi L et al. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. J. Virol. 79(23), 14614–14621 (2005).Crossref, Medline, CAS, Google Scholar 5. Cockrell AS, Peck KM, Yount BL et al. Mouse dipeptidyl peptidase 4 is not a functional receptor for Middle East respiratory syndrome coronavirus infection. J. Virol. 88(9), 5195–5199 (2014).Crossref, Medline, Google Scholar 6. Belouzard, S., Chu, V. C. & Whittaker, G. R. Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proc. Natl Acad. Sci. USA 106, 5871–5876 (2009). Figure 2. The genotype and phylogenetic tree of .coronaviruses Figure 1. Imagination of an artificial synthetic protein (red) combining with coronavirus instead of human cells to block infection )Source = British Columbia, Canada(
