**2. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)**

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has aroused the attention of the world since 2019 [9]. It is the third severe epidemic of

beta-coronavirus (β-CoV) after the severe acute respiratory syndrome (SARS) and the middle east respiratory syndrome (MERS) [10]. SARS-CoV-2 is an enveloped, positive single-stranded RNA virus [11]. Its genome consists mainly of open reading frames (ORF). ORF1ab represents 67% of the viral genome which encodes the synthesis of polyproteins (nonstructural proteins) in the infected cell (1a, 1ab). The viral structural proteins are synthesized from the last 33% ORFs [12–14]. SARS-CoV-2 has four structure proteins: spike (S) glycoprotein, envelope glycoprotein (E), membrane glycoprotein (M), and nucleocapsid protein (N) [15–17]. The pathogenesis of SARS-CoV-2 starts by binding the spike protein (S) with angiotensin-converting enzyme 2, (ACE2). Then synthesis of different viral structural, nonstructural, and extra proteins take place in the infected cells. This is associated with inhibition of the host innate immunity at the early phase of the infection. Then the virus acts against adaptive immunity and spreads in the whole body with subsequent acute and chronic complications. Autoinflammation, immunosuppression, and hyperimmune response may occur [18]. The virulence of SARS-CoV-2 is mediated by the downregulation of pattern recognition receptors (PRRs), which triggers the anti-viral innate immunity mainly interferons (IFNs) release [18, 19]. In addition, the virus stimulates polyclonal activation and apoptosis of lymphocytes leading to pathological activation of macrophages, and immunosuppression [20]. The rapid replication rate of the RNA genome increases the incidence of mutations due to replication errors mediated by RNA polymerase or reverse transcriptase [21, 22]. Mutations in S-protein significantly alter viral pathogenesis [23]. This may impair the immune response to vaccines [24]. Treatment of SARS-CoV-2 has two pathways: the first is to overcome the viral infection either by blocking cell binding, replication, or direct viral effect on tissues. The second pathway is to counteract the overwhelming viral-induced immune response [25]. For blocking viral entry, many agents coexist, such as umifenovir [26, 27], soluble recombinant hACE2, and specific monoclonal antibodies [28, 29]. Several drugs were tried to inhibit viral replication, such as remdesivir [30] favipiravir [31], ribavirin, lopinavir, and ritonavir [32]. For immune modulation, a lot of drugs were introduced, such as dexamethasone [33], tocilizumab, interleukin-6 (IL-6) receptorspecific antibody [34, 35], Eculizumab, a complement 5 inhibitor [36], INF [37, 38], baricitinib, protein kinases inhibitors [39], and imatinib the Abl tyrosine kinase inhibitor (ATKI) [40]. Multiple COVID-19 vaccines have been developed and others are undergoing clinical validation. Despite improving disease morbidity, the vaccines failed to prevent SARS-CoV-2 infection [41, 42]. The drop in anti-SARS-CoV-2 neutralizing antibodies level explains the postvaccination reinfection [43]. Currently, there is no curative anti-SARS-CoV-2 treatment.
