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Genetic and structure of novel coronavirus COVID-19 and molecular mechanisms in the pathogenicity of coronaviruses

Yousefi, Bahmana,c; Eslami, Majidb,c

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Reviews and Research in Medical Microbiology: January 2022 - Volume 33 - Issue 1 - p e180-e188
doi: 10.1097/MRM.0000000000000265
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In the past 20 years, China has the place of emergence of several viral diseases, including avian influenza in 1997, severe acute respiratory syndrome (SARS) in 2003, and severe fever with thrombocytopenia syndrome in 2010 [1]. The recent crisis was the outbreak of novel coronavirus from emerged Wuhan in central China, referred to as 2019 novel coronaviruses (2019-nCoV) (also Wuhan virus), has recently caused a pandemic scale of pneumonia in humans and resulted in a huge threat to the global public and a high number of hospitalizations [2].

This virus is currently related to SARS coronavirus (SARS-CoV). With a similar chain of procedures as the origin of SARS-CoV, it seems the infection origin of 2019-nCoV s to be linked to contact with animals [3]. In late December 2019, Wuhan Municipal Health Commission reported 27 cases of viral pneumonia hospitalization, most of them had a history of exposure to the virus through poultry, bats, snakes, and other wildlife animals [4]. Coronaviruses consist of a huge various family of viruses. They can be categorized into four genera: alpha coronaviruses, beta coronaviruses, gamma coronaviruses, and delta coronaviruses. Alpha coronaviruses [human coronaviruses (HCoVs) NL63], whereas the beta coronaviruses include the best-known SARS-CoV and the Middle East respiratory syndrome-related coronavirus (MERS-CoV) [5]. Based on nucleic acid sequence similarity, the newly identified 2019-nCoV is a beta coronavirus although with only nearly 80% likeness at the nucleotide level. As a concern, it is critical to developing actual measures to control this novel coronavirus based on its pathogenesis [6].

These cause damage to the lungs, which leads to fluid leaking from small blood vessels in the lungs. The fluid collects in the lungs’ air sacs or alveoli. This makes it difficult for the lungs to transfer oxygen from the air to the blood. While there's a shortage of information on the type of damage that occurs in the lungs during 2019-nCoV [7]. In this review, we will describe specific genomic characterization, phylogenetic, structural features as well as mechanisms of its pathogenesis of this 2019-nCoV, providing important information on the origins and cell receptor binding of the virus determine right target antigens involves designing the vaccine constructs as well as viral proteins that are targeted by the immune system. Therefore, these vaccines can improve into clinical trials in humans to induce the expected immune response and protection for vaccination of the population. The purpose of this review was to investigate the genetic and structure of novel coronavirus COVID-19 and molecular mechanisms in the pathogenicity of coronaviruses.

Latest coronavirus statistics

According to the latest WHO reports so far 11/25/2020, 218 countries and territories worldwide have confirmed coronavirus infection, with a total of 60 380 105 confirmed COVID-19 cases originating from Wuhan, China, and 1420 047 deaths were recorded. With 12 978 833 cases, the United States has the highest number of cases of coronavirus, followed by India, Brazil, Russia, and France with 9257 945, 6127 819, 2162 503, and 2153 815, respectively. In terms of mortality after the United States, with 266 285 cases Brazil and India with 170 199 and 135 165 deaths have the highest death rate. Of all COVID-19 patients, 97% recovered and only 3% died. Since the first death on 11 January, the mortality rates are still rising. The first case of death outside China was also a 44-year-old man from Wuhan, China, who died on 2 February in the Philippines. Overall, there was a quantity growing by 7% every period with a growth factor of 1.07 indicating an increase in mortality [8,9].

Most of those recovered from the disease also came in second and third, after India with 8673 328 cases, followed by the United States and Brazil with 7641 913 and 5476 018 cases, respectively. The COVID-19 mortality rate is 8% which is lower than SARS (10%) and MERS (34%), but the death rate could change because the virus can mutate, according to the epidemiologist. Symptoms of the new coronavirus (2019-nCoV) may vary from 2 to 14 days but cases up to 27 days have been reported (mean incubation period is 2.5 days); however, the virus is highly contagious and the patient may have no symptoms of it doesn’t show itself [8,9].

According to the latest statistics from China's National Health Commission, about 80% of those who died were over 60 years old, and 75% of them had cardiovascular disease and diabetes. Most cases and deaths are in patients with cardiovascular disease, diabetes, chronic respiratory diseases such as asthma, hypertension, and cancer. The average age of patients outside of China was 45 years, ranging from 2 to 74 years, with 71% of men having the disease. It is therefore concluded that individuals of any age can be infected by 2019-nCoV [8,9].

Pathogenesis of disease

Four HCoV including HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 (Hong Kong University) are prevalent and typically cause common cold symptoms in immunocompetent individuals [10]. Mechanisms that SARS-CoV caused more severe pathogenicity are so far not completely understood. Moreover, extensive lung damage in SARS-CoV-infected patients appears to be linked with high initial virus loads, enhanced monocyte, macrophage, and neutrophil infiltration in the lungs, and high levels of proinflammatory cytokines and chemokines in blood circulation. SARS-CoV pathogenesis effects may consequence in a mixture of direct (virus-induced cytopathic effects) and indirect (immunopathology-induced effects) [11,12]. Throughout SARS-CoV infection discovered increased levels of TNF-α, CXCL-10, IL-6, and IL-8, probable donated to the poor prognosis in SARS-CoV infections. Also, high enhanced proinflammatory cytokines including IL-1, IL-6, IL-12, IFN-γ, transforming growth factor-β, and chemokines (CCL2, CXCL9, CXCL10, and IL-8) were established in patients with SARS with severe disease in comparison with individuals with uncomplicated participants [13]. It has also been revealed that SARS-CoV infections result in a delayed expression of type I interferon. Because delayed interferon type I transduction, which was associated with vigorous virus replication, stimulates the gathering of pathogenic immune infiltration cells (monocyte and macrophages), consequential in raised vascular leakage, and weakened virus-specific T-cell responses [14].

MERS-CoV infects many human immune cells, including dendritic cells, macrophages, and T cells [15]. Dendritic cells and macrophages result after infected with this virus produce robust levels of proinflammatory factors, such as TNF-α, IL-6, CXCL-10, CCL-2, CCL-3, CCL-5, and IL-8, that lead to immune cell infiltration into the lower respiratory region of infected individuals and the observed caused inflammation as well as tissue destruction. Extrinsic and intrinsic pathways mediated apoptosis, which may contribute to virus expansion and severe immunopathology effects. The genome sequence analysis of 2019-nCov in very early during the outbreak revealed that the 2019-nCoV belongs to the beta coronavirus, with a nearly 79% nucleotide uniqueness to SARS-CoV and 51.8% identity to MERS-CoV. Moreover, these analyses described that 2019-nCoV is 96% identical across the entire genome to a bat coronavirus. 2019-nCoV after entering the lungs of the causes cytopathic. The major clinical signs causing by 2019-nCoV infection include fever, dry cough, myalgia, fatigue, and diarrhea also many patients have developed dyspnea and lymphopenia [16,17].

Acute respiratory distress syndrome, acute cardiac injury, and secondary infections are some complications of 2019-nCoV-infected individuals. All reported cases, as well as asymptomatic patients, had atypical findings concerning the chest computed tomography (CT) as indicated by bilateral ground-glass opacity and CT images findings of extremely ill patients shown that these patients requiring ICU [18].

Initial serum competent analysis revealed the higher levels of IL-1β, IL-1Rα, IL-7, IL-8, IL-9, IL-10, FGF, GCSF, GMCSF, IFNγ, IP10, MCP1, MIP1A, MIP1B, PDGF, TNF-α, and VEGF in 2019-nCoV-infected patients. Moreover, hospitalized 2019-nCoV patients in the ICU ward showed enhanced concentration levels of IL-2, IL-7, IL-10, GSCF, IP10, MCP1, MIP1A, and TNF-α than non-ICU patients. These outcomes suggest that immunopathology events may also play a significant role in the development of disease harshness [19,20].

SARS-CoV which causes SARS has unique pathogenesis because it causes both upper and lower respiratory tract infections [11]. It has been reported that 2019-nCoV uses the same cell entry receptor, angiotensin (Ang)-converting enzyme 2 (ACE2), to infect humans, as SARS-CoV, so the clinical similarity between the two viruses could be expected, particularly in severe cases. Notably, there are signs, from what is still very limited data, that the clinical features of 2019-nCoV seem to be more variable. The severity of the disease is most often an important indirect factor in a virus's ability to spread. Because coronaviruses have error-prone RNA-dependent RNA polymerases, this reason, mutations, and recombination events frequently occur and resulting in a variety that is closely related to the adaptive evolutionary capacity of this virus to cause disease [21,22]. Prior research studies have shown that SARS-CoV mutated over the 2002–2004 epidemic to well bind to its cellular receptor and replication in human cells and afterward enhancing virulence factors [23]. It seems that 2019-nCoV works like SARS-CoV to adapt to the human host and whether this would increase the change of its virulence factors [24]. By contrast, MERS-CoV has not mutated events since it was revealed, which may be due to that the functional cellular receptor (CD26) used by MERS-CoV is unique [25]. Remarkably, ACE2, the receptor protein is abundantly present in humans in the epithelia of the lung and small intestine for both virus SARS-CoV and 2019-nCoV, and that's why coronaviruses can infect the upper respiratory and gastrointestinal system in mammals. Moreover, ACE2 is highly expressed in extrapulmonary tissues including the heart, kidney, endothelium, and intestine on the luminal surface of intestinal epithelial cells [21].

Spike glycoprotein provides a crown-like appearance for coronaviruses to enter into host cells. Spike glycoprotein of the amino acid sequence consists of a large ectodomain, a single-pass transmembrane anchor, and a short C-terminal intracellular tail. The ectodomain contains a receptor-binding unit S1 and a membrane-fusion unit S2. S1 binds to a specific cell surface receptor, and S2 fuses the host cell and viral membranes, enabling the entry of viral genomes into host cells [26]. Host receptor recognition is a determinant for virus infection as mentioned above ACE2, the receptor for 2019-nCoV, from human, Rhinolophus sinicus bat, civet, swine. The other research studies reported or predicted human ACE2 usage of 2019-nCoV in a similar way to SARS-CoV mainly based on the coronavirus spike (S) glycoproteins. Considering the fact that the S proteins mutate and gain the capability to recognize host receptors among species [27]. A comparison of different conditions of three diseases caused by coronaviruses (COVID-19, SARS, and MERS) are shown in Table 1.

Table 1 - Comparison of different conditions of three diseases caused by coronaviruses (COVID-19, severe acute respiratory syndrome, and Middle East respiratory syndrome).
VirusConditions Novel coronavirus (2019-nCoV or COVID-19) SARS (SARS-CoV) MERS (MERS-CoV)
Genus of virus Betacoronavirus Betacoronavirus Betacoronavirus
Subgenus of virus Sarbecovirus Sarbecovirus Merbecovirus
Incubation period (typical cases) 2–14 or 0–27 Days 2–7 Days, as long as 10 days 5 Days (range: 2–14)
Death rate 3% 9.6% 34%
Number of countries spread 218 29 27
Human–human transmission Yes Yes Yes
Nosocomial transmission Yes Yes Yes
Main feature ARDS/pneumonia ARDS/pneumonia ARDS/pneumonia
Outbreak started Wuhan, China Guangdong, China Middle EastSaudi Arabia
Starting year December 2019 September 2003 September 2012
Number of patients 60 380 105 8473 2494
Number of deaths 1420 047 774 858
Low R 0 1.5 and 3.5 Approximately 4 Approximately 1
Source of disease Unclear, bat suspected Bats and civet cats Dromedary camels
Receptor ACE2 ACE2 DPP4 or adenosine deaminase complexing protein 2 or CD26
Low R0: Each person with the disease transmits it to only one other person. 2019-nCoV, 2019 novel coronaviruses; ACE2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; DPP4, dipeptidyl peptidase-4; MERS, Middle East respiratory syndrome; SARS, severe acute respiratory syndrome.

Diversity, composition, and genome structure of coronavirus

The Coronaviridae family consists of the subfamilies of the Coronavirinae and Torovirinae viruses. The enveloped RNA viruses and +ssRNA are approximately 26–32 kb in genome size. The four genera of Coronaviridae include alpha, beta, gamma, and delta coronavirus, in which alpha and beta coronavirus are found in mammals, and gamma and delta coronavirus are found in birds. Bats appear to be the natural reservoir of coronaviruses and are responsible for the spread of CoV viruses [28].

Alpha coronaviruses include HCoV-229E, HCoV-NL63, and transmissible gastroenteritis virus. Beta coronavirus containing Bat-SL ZC45, Bat-SL ZXC21, 2019-nCoV, SARS-CoV, MERS-CoV, HCoV-OC43, coronaviruses identified by HKU-1 and murine hepatitis virus-A59. Gama coronaviruses include IBV (infectious bronchitis virus) and SW1 and, delta coronaviruses also contain HKU-11 and HKU-17 [28].

Coronaviruses contain four structural proteins and the virus envelope includes spike-shaped glycoproteins (S), envelope proteins (E), membrane proteins (M), and nucleocapsid (N). The role of proteins is in the binding and entry of the virus into the host cell [29]. The viral transcriptase-replicase complex is made up of 16 nonstructural proteins (nsp1–16) encoded by pp1a and pp1ab polypeptides. Nonstructural proteins are involved in the formation of rough endoplasmic reticulum-derived double-membrane vesicles that are also sites of virus replication and transcription. The coronavirus also encodes a proofreading exoribonuclease (ExoN) using nsp14, which reduces the accumulation of mutations in the RNA genome. CoV spike protein is also required for entry into the host cell. The S1 spike subunit contains the receptor-binding domain (RBD). Virus entry is via the host and viral membranes and fusion of the S2 protein spike subunit. The SARS-CoV virus uses the ACE2 receptor to bind to the host cell, which contains a variety of respiratory epithelial cells, alveolar macrophages, and monocytes [30,31].

The CoV genome and subgenome contains at least six open reading frames (ORFs). The first ORF contains ORF1a1b, which forms two-thirds of the genome and encodes 16 nsp. A frameshift between ORF1a and ORF1b results in the production of two pp1a and pp1ab polypeptides. These polypeptides are processed by chymotrypsin-like protease (3CLpro) or main protease (Mpro) and one or two papain-like proteases at 16 nsp. The other ORFs that make up the remaining one-third of the genome encode four structural proteins of spike, membrane, envelope, and nucleocapsid. Despite these four proteins, different CoV encodes other structural and accessory proteins such as hemagglutinin-esterase proteins, 3a/b protein, and 4a/b protein [32,33]. Nonstructural proteins (nsps) of coronavirus and their functions are shown in Table 2.

Table 2 - Nonstructural proteins of coronavirus and their functions.
nsps (Molecular weight) Functions References
nsp1–9 kD α-CoVs and β-CoVs encode nsp1 whereas γ-CoVs and δ-CoVs lack nsp1 Blocks host cell translation Cellular mRNA degradation Chemokine dysregulation Highly divergent among CoVs Inhibiting IFN signaling Modulate host and viral gene expression during CoV infection Promotes cellular/host mRNA degradation Potential virulence factor Results in blocking the innate immune response Regulation of host and viral gene expression Suppresses host gene expression, including that of type I interferon Suppress host protein synthesis Target for CoV vaccine development [34–37]
nsp2–65 kD Binds to prohibitin proteins Dispensable for viral replication May play a critical adaptor/regulatory role for nsp3 function Pivotal role in the viral life cycle Viral infection [28,38]
nsp3–200 kD ADRP activity, promotes cytokine expression Binds to viral RNA, nucleocapsid protein, as well as other viral proteins, and participates in polyprotein processing Blocks host innate immune response Blocking host innate immune response Cleaves viral polyprotein Essential component of the replication/transcription complexMultifunctional protein comprising up to 16 different domains and regions PLPro PLPro/Deubiquitinase domain Polypeptides cleaving Promoting cytokine expression The papain-like protease of nsp3 is an established target for new antivirals Through its de-ADP-ribosylating, deubiquitinating, and de-ISGylating activities, nsp3 counteracts host innate immunity Ubl1 (ubiquitin-like) and Ac domains, interact with N protein Ubl2, NAB, G2M (coronavirus group 2 marker domain), SUD, Y domains, unknown functions [28,39–41]
nsp4–54 kD Assembly of murine coronavirus DMVs DMV formation Interaction with nsp3 through H120&F121 in nsp4 is crucial for viral propagation Potential transmembrane scaffold protein [42,43]
nsp5–32 kD Cleaves viral polyprotein Cysteine protease 3CLpro Inhibiting IFN signaling Mpro Novel targets for nonactive site inhibitors Polypeptides cleaving [44–46]
nsp6–30 kD Complex with nsp3 and nsp4: DMV formation Potential transmembrane scaffold protein Restricting autophagosome expansion [41,47]
nsp7–9 kD Cofactor with nsp8 and nsp12 Complex with nsp8: primase Forms hexadecameric complex with nsp8 May act as processivity clamp for RNA polymerase [30,48,49]
nsp8–21 kD Cofactor with nsp7 and nsp12 Complex with nsp7: primase Forms hexadecameric complex with nsp7 May act as processivity clamp for RNA polymerase [30,50]
nsp9–12 kD Dimerization and RNA binding Replicase protein RNA-binding protein [51]
nsp10–14 kD Cofactor for nsp16 and nsp14 Complex with nsp14: replication fidelity Critical cofactor for activation of multiple replicative enzymes Forms heterodimer with both and stimulates ExoN and 2-O-MT activity Scaffold protein for nsp14 and nsp16 [52–54]
nsp11–2 kD EndoU Short peptide at the end of orf1a [55,56]
nsp12–105 kD NiRAN, nidovirus RdRp-associated nucleotidyltransferase Primer dependent RdRp RdRp [57,58]
nsp13–66 kD HEL1, superfamily 1 helicase RNA helicase RNA 5′-triphosphatase activity ZBD [59–61]
nsp14–58 kD ExoN activity is important for proofreading of the viral genome Fidelity control Involved in mRNA capping N7-MT, N7-methyltransferase N7 MTase and 3′-5′ exoribonuclease N7 MTase (viral exoribonuclease) adds 5′ cap to viral RNAs Viral EndoU (ExoN) [62–64]
nsp15–38 kD EndoU, uridylate-specific EndoU NendoU (EndoU was considered a nidovirus-specific marker, EndoU) Viral EndoU [65]
nsp16–33 kD 2′-O-MT Involved in mRNA capping Shields viral RNA from MDA5 recognition [59,66]
2′-O-MT, 2′-O-methyltransferase; 3CLpro, chymotrypsin-like protease; ADRP, ADP-ribose-1′-phosphate; CoV, coronaviruses; DMV, double-membrane vesicle; EndoU, endoribonuclease; MDA5, melanoma differentiation-associated protein 5; Mpro, main protease; NAB, nucleic acid binding; nsps, nonstructural proteins; PLPro, papain-like proteinase; RdRp, RNA-dependent RNA polymerase; SUD, severe acute respiratory syndrome unique domain; ZBD, zinc-binding domain.

Angiotensin-converting enzyme

Similar to SARS-CoV, 2019-nCoV uses ACE2 as the RBD for its spike protein. However, the RBDs of these sequence identity among two coronaviruses share are 72% amino acid. Moreover, the 2019-nCoV receptor has a higher affinity for ACE2 compared with SARS-CoV. Includes a distinct loop with flexible glycyl residues replacing rigid prolyl residues in, and molecular modeling indicated that the ACE and ACE2, belonging to the ACE family with opposing physiological roles. ACE cleaves Ang I to generate Ang II, the peptide which binds to and activates Ang II type I receptor (AT1R) to constrict blood vessels, thereby elevating blood pressure (BP) [67,68]. By contract, ACE2 inactivates octapeptide Ang II while generating its metabolite Ang1–7, a heptapeptide having a potent vasodilator function via activation of its Mas receptor, and thus serving as a negative regulator of the renin–Ang system (RAS). It has been demonstrated that the binding of the coronavirus spike protein to ACE2, its cellular binding site, leads to ACE2 downregulation, which in turn results in excessive production of Ang by the related enzyme ACE, while less ACE2 is capable of converting it to the vasodilator heptapeptide Ang1–7. This, in turn, contributes to lung injury, as Ang-stimulated AT1R results in increased pulmonary vascular permeability, thereby mediating increased lung pathology. The physiological role of Ang1–7 has not obvious but it generally appears to oppose the pressure, proliferative and profibrotic actions of Ang II and acts through its G-protein-coupled receptor. This would suggest that ACE and ACE2 might act as counterbalances in the RAS. Tissue distribution correlates with sites ACE2 appears and the following infection death rate in SARS-CoV disease nearly is 10%. The RBD for ACE2 was probably located between residues 272 and 537 of the spike glycoprotein of the SARS-CoV receptor and showed that the. Farzan's group described the recognition region within a residues 318–510 of spike glycoprotein [69,70].

The other zinc peptidase is aminopeptidase N (APN), which acts as the receptor for several other coronaviruses, and distribution sites of this peptide can be associated with infection. However, away from the zinc-binding region APN and ACE2, have shown sequence homology and dissimilar membrane topology [71].

Angiotensin-converting enzyme 2 receptor antagonists

The interaction sites among ACE2 and SARS-CoV have been recognized at the atomic level and from studies to date should also hold for interactions between ACE2 and SARS-CoV-2 [72].

Two unpredicted inhibitory binding sites of ACE2 (interaction with antibodies or small molecules), including inhibitor binding that induced a great conformational alteration in the enzyme that aligns vital residues for catalysis activation, the inhibitor binds to the enzyme in an opposite orientation from that expected from the binding of the ACE -inhibitors lisinopril to the active site of ACE [73].

Losartan, telmisartan, olmesartan (and extra AT1R antagonists) are widely applied in the clinic since the 1990s for control of hypertension and kidney disorders and are known as safe drugs that are rarely implicated in adverse drugs events. The AT1R antagonists such as losartan and olmesartan, usually useful after myocardial infarction for reducing BP in hypertensive patients, and increase cardiac ACE2 in coronary artery ligation following treatment. Losartan was also revealed to increase renal ACE2 expression in chronically treated rats. Higher urinary ACE2 levels were detected in hypertensive patients treated with another AT1R antagonist, olmesartan. Collected information showed that chronic AT1R antagonists result in ACE2 upregulation in humans and animal models [74].

AT1R antagonists apply such as losartan and telmisartan for SARS-CoV-2 treatment for treating patients before the development of acute respiratory syndrome remains unproven until tried. At the time of writing this brief commentary, the end of the COVID-19 epidemic is not in sight and drastic actions are required (and being done) for containing its spread and death toll. Therefore, infected individuals who were before their diagnosis had received AT1R antagonists (for the care of their hypertension, diabetic kidney disease, or other signs) obtained protection from severe symptoms and better disease outcome. At the same time, efforts must be made for developing a 2019-CoV2 vaccine. Several potent and relatively selective inhibitors of ACE2 have been described, and the modeling of the active site of ACE2, based on the recently reported structure of human ACE, will facilitate the development of new classes of specific inhibitors [74–76].

Spike protein-based vaccine approaches

Progress in spike1 subunit protein-based vaccine might depend on ACE2 is the 2019-CoV2 receptor. Viral replication in the presence of ACE2 in cell lines may be the well organized approach for large-scale vaccine production [77].

Inhibitory effects of transmembrane protease serine 2

Recently established that early spike protein priming by transmembrane protease serine 2 is vital for entry and viral spread of 2019-CoV2 through interaction with the ACE2 receptor [77].

Delivering soluble form of angiotensin-converting enzyme 2

Soluble ACE2 may competitively bind with 2019-CoV2 and survive cellular ACE2 activity which negatively regulates the RAS to protect the lung from damage. Certainly, as mentioned above enhanced ACE activity and reduced ACE2 availability contribute to lung injury during acid-induced and ventilator-induced lung injury. Thus, conduct soluble ACE2 may utilize to decline viral entry into cells as well as viral spread and also protect the lung from damage [78]. The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, ACE2, fused to an immunoglobulin Fc domain (ACE2-Fc), providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity. The sequence of the ACE2-Fc protein is provided to investigators, allowing its possible use in recombinant protein expression systems to start producing drugs today to treat patients under compassionate use, while formal clinical trials are later undertaken. Such a treatment could help infected patients before a protective vaccine is developed and widely available in the coming months to years [79,80].

Conclusion and future perspectives

Together with the other two highly pathogenic coronaviruses, the SARS-CoV and MERS-CoV, 2019-nCov and other yet to be identified coronaviruses pose a global threat to public health. 2019-nCoV outbreak from Wuhan, China offered a respiratory viral pandemic that currently there are no effective therapies for this infection. Despite a crucial need to find options to help these patients and prevent potential death. For this reason, vaccine research should be pursued intensely, until the infection can be controlled with a protective vaccine to prevent 2019-nCoV infection. By considering the options of drug repurposing, developing neutralizing mAb therapy, and an oligonucleotide targeting of the viral RNA genome, emphasizing these approaches. Moreover, the soluble version of the viral receptor that's mean (ACE2) to blocks 2019-nCoV entry, through bonded to an immunoglobulin Fc domain (ACE2-Fc), providing a neutralizing antibody that can provide avoid viral outflow, also helping to employee the immune system to shape long-lasting immunity. However, existing data are consistent with identification ACE2 as a SARS-CoV receptor, but there might be existence unknown other receptors or coreceptors for this virus that are yet to be discovered. Effective therapies against SARS are urgently required to interrupt further major outbreaks occurrence.


This research is not supported by a specific project grant.

Author contribution: M.E.: Investigate and supervised the findings of this work, wrote the article. Processed the experimental data. Supervised the project. Designed the model and the computational framework and analyzed the data. B.Y.: Designed the study, helped supervise the project, conceived the original idea. Processed the experimental data. Developed the theoretical framework. Designed the model and the computational framework and analyzed the data.

Conflicts of interest

There are no conflicts of interest.


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