Beginning in February 2020,new corona virus outbreaks has been declared by the world Health organization(WHO) as a “public health emergency of international concern”. (1)Coronavirus disease 2019(COVID-19) is an infectious disease which is caused by a newly identified coronavirus with the name of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2).Members of the coronaviridae family are enveloped single-stranded RNA, positive-sense, viruses (2). Researchers called this family as a coronavirus because of virus surface is surrounded by a ring of projections (3). The new coronavirus is widespread,because of easily and quickly transmitting of this virus through discharge from the nose or droplets of saliva which can be spread by sneeze or cough of a person who is infected with this virus.some different complications from this virus are cough,fever,fatigue,headache,hemtopoysis and diarrhea.(4)
The procedure of viral infection, including intracellular transport of virions, proliferation and assembling of virions in the infected host cells can significantly influenced by structural protein such as E protein (small membrane protein), M protein (the membrane protein), and S proein (spike protein) which can be shared on the memberane of the virus. Another regulators are functional proteins and some proteases .functional proteins are
Helicase, RdRp protein (RNA-dependent RNA polymerase), 3-CLpro protein (3-chymotrypsin-like protease), and PLpro protein (papain-like protease) which play a crucial role in infection of covid 19.(5) Attachment of spikes of covid-19strongly to a cell protein with name of ACE2, which is identify on the surface of humman cells, is the first step of viral pathogenesis and likely is very vital in transmission of this virus from one person to another.(6)
ACE2 expressing target cells (such as alveolar type 2 cells) are the aim of This virus and leads to infection. anti-viral IFN responses may fade the virus Virus may fade which is result in uncontrolled viral replication. Overproduction of pro-inflammatory cytokines happen after neutrophils and monocytes/macrophages influx and leads to cytokine storm. Cytokine storm can can impact on lungs cell and immunopathology of lung can be the impact of cytokine storm . Th1/Th17 cells response may be activated and contributes to exacerbate inflammatory responses in host. Specific antibodies produced by B cells/plasma cells against COVID-19 virus may help neutralize virus. COVID-19 seem to share the entry receptor of ACE2 (7-10).
In lung, ACE2 can be expressed by Type 2 alveolar cells and monocytes/macrophages . If ACE2 is minimally expressed in the potential target immune cells, there is possibility that other receptors may exist, or other cellular entry mode is utilized such as antibody-dependent enhancement. Innate immune system cells identify the virus’s influx by PAMPs (pathogen associated molecular patterns). TLR3, TLR7, endosomal RNA receptors, and RIG-I/MDA5 (the cytosolic RNA sensor) can recogonize PAMPs in the form of viral genomic RNA or the intermediates during viral replication including dsRNA.
This diagnosed cascade can active the down-stream signaling cascade, i.e. NF-κB and IRF3, accompanied by their nuclear translocation. these transcription agents promote expression of some pro inflammatory cytokines immune system such as type I interferon and this initial responses contain the first step of defense in front of COVID-19 (7, 27). Type I interferon can through IFNAR especially IFNAR2, can the JAK-STAT pathway, this pathway can phosphorylate STAT1 and STAT2. STAT1/2 make a complex with IRF9, and this complex move to nucleus to initiate the intracellular expression .It also recommended that IFN can have a good effect if it utilize at the first step of diseases. (7, 28, 29).
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