# Honey as an Adjuvant in the Treatment of COVID-19 Infection: A Review
## 3 SARS-CoV-2 Overview and Vaccines Mechanism of Actions  
The SARS-CoV-2 virus mostly targets the cells of the lower respiratory tract (due to its easy binding to epithelial cells), and replicates and migrates to the airways and alveolar epithelial cells in the lungs [52]. Extensive efforts have been made to characterize this virus through genomic sequence studies, mainly focusing on determining the viral protein structure [53; 54; 55]. Full genome-sequencing analysis has classified SARS-CoV-2 as a new member of the betacoronavirus genus, which includes SARS-CoV, MERS-CoV, and bat SARS-related coronaviruses (SARS-CoV) [56]. Like other CoVs, its genome encodes \begin{table}
\begin{tabular}{c c c c c c c c c c} \hline \hline
**Geographical** & \multicolumn{8}{c}{**Minerals and Trace Elements (mg/kg)**} & \multicolumn{1}{c}{**Ref.**} \\ \cline{2-10}
**Origin** & **Fe** & **Zn** & **Cu** & **Mn** & **Na** & **K** & **Ca** & **Mg** \\ \hline Argentina & 2.07–4.5 & 0.51–2.75 & 0.09–1.19 & 0.14–8.84 & 4.88–105.95 & 134.1–2813.3 & 1.97–18.97 & 3.01–75.38 & [42] \\ \hline Bulgaria & 0.71–19.25 & 0.71–1.71 & 0.05-0.49 & 0.31–4.7 & 6.3–20.2 & 136–1900 & 24–94 & 8.3–48 & [43] \\ \hline Ecuador & nd & nd & nd & nd & 9.0–23.0 & 7.0–133.0 & 15.0–31.0 & 4.0–11.0 & [13] \\ \hline Greece & 1.03–6.30 & 0.89–1.81 & 0.14–0.52 & 0.15–1.46 & 10.3–42.0 & 391–2494 & 18.0–78.0 & 6.8–63.6 & [44] \\ \hline Pakistan & 0.04–0.19 & - & - & 1.05–3.11 & 211.6–579.6 & 166.5–465.66 & 0.5–0.73 & - & [45] \\ \hline Pakistan & 2.98–16.2 & 1.11–4.1 & 0.08–0.33 & 0.12–0.95 & 77.5–200 & 225–439 & 46.1–98.1 & 31.3–73.8 & [46] \\ \hline Poland & nd–16.1 & nd–9.93 & nd–1.82 & - & 0.38–89.6 & 7.7–2612.2 & 3.3–159.2 & 0.07–19.83 & [47] \\ \hline Slovakia & 1.02–5.14 & 0.16–1.30 & 0.045–2.01 & 0.44–15.1 & 8.49–10.3 & 0.33–3.71 & 20.3–36.6 & 12.5–65.0 & [48] \\ \hline Tunisia & 0.83–3.54 & 0.42–2.06 & 0.12–0.34 & - & 251.34–521.22 & 172.48–976.75 & 113.85–221.07 & 37.32–78.12 & [30] \\ \hline Turkey & \textless{}0.001–7.25 & \textless{}0.001–0.24 & \textless{}0.001–0.93 & \textless{}0.001–0.27 & 0.48–13.1 & 1.18–268 & 0.77–4.5 & - & [49] \\ \hline Turkey & BDL–14.0 & BDL–1.98 & BDL–0.46 & BDL–0.82 & - & - & - & - & [50] \\ \hline \hline \end{tabular} BDL–bellow the detection limit; nd–not detected.  
\end{table} 
Table 3: Mineral composition and trace elements (mg/kg) of honey from different geographical origins. sixteen non-structural replicase proteins (nsp 1-16), nine accessory proteins (ORF) and four structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins [56; 57]. Among the structural proteins, the S protein plays an important role in virus attachment, fusion, entry, and disease pathogenesis, since it mediates viral access into the host cells by binding to a host receptor through the receptor-binding domain (RBD) in the S1 subunit and fusing the viral and host membranes through the S2 subunit 9. Thus, the S protein has been selected as a preferred target for the development of antibodies, entry inhibitors and vaccines [58; 59]. In SARS-CoV-2, as in SARS-CoV, this protein binds to the receptor angiotensin-converting enzyme 2 (ACE2). Spike RBD-ACE2 binding happens not only with the human ACE2 (hACE2), but also with the ACE2 from other animals, such as pig, ferret, rhesus monkey, civet, cat, pangolin, rabbit, and dog [52]. The importance of this interaction is highlighted by the mutations on the spike protein that contribute to a different behavior of SARS-CoV-2 and cause different variants of the disease. [PERSON] and co-workers [60] evaluated mutation effects on the spike and on the hACE2. The authors studied five common RBD mutations (K417N, K417T, N501Y, E484K, and S477N) and two common hACE2 mutations (S19P and K26R), individually and in combination with the RBD-hACE2 interaction. The mutations selected were identified in SARS-CoV-2 Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P1) variants.