**4.1** *Citrus* **fruits and (COVID-19)**

The potential significance of diet in the mitigation of coronavirus infection 2019 (COVID-19) has been undervalued so far among the different options. Foods contain usually compounds that may have a health benefit, and some of these chemicals may have antiviral properties and may be useful in altering the immune function and source of antioxidants from the oxidative stress generated by infection [37]. *Citrus* fruits are high in flavanones, vitamin C, and anthocyanins the most abundant of which are naringin and hesperidin, both of which have antioxidant and antiinflammatory qualities [38–40]. Fibers, such as pectin, which is more abundant in the solid section, aid in the regulation of intestinal activities and the prevention of LDL cholesterol absorption. *Citrus* may also be effective in reducing the risk and cure of viral diseases [37].

**Figure 2.**

*Health benefits of* Citrus *and its constituent [27, 33–36].*

#### Citrus*: An Overview of Food Uses and Health Benefits DOI: http://dx.doi.org/10.5772/intechopen.106420*

The revelation that hesperidin possesses a chemical-physical structure that allows it to attach to critical proteins involved in the SARS-CoV-2 virus's activity has piqued scientists' curiosity. At least six investigations returned similar outcomes [41–45].

Wu and collaborators [41] for binding to SARS-CoV-2 proteins, evaluated 1066 natural compounds with the ability of antiviral effects, along with 78 antiviral medicines that have previously been described. The best option for bonding to the "spike" was hesperidin. At the point when the ACE2 — RBD complex is superimposed over the hesperidin — RBD complex, there is critical hesperidin contact with the ACE2 interface, showing that hesperidin may alter ACE2's interaction with RBD. Another thorough molecular docking investigation of the hesperidin-Mpro interaction was published recently [44]. The lowest binding energy (showing the most affinity) was revealed to be rutin (9.55 kcal/mol), followed by hesperidin (9.02 kcal/mol), emetine (9.07 kcal/mol), ritonavir (9.52 kcal/mol), and indinavir (8.84 kcal/mol) in a screening of 33 natural and already known antiviral compounds. THR45, THR25, THR24, CYS145, HIS4, and SER46 are among the amino acids to which hesperidin forms hydrogen bonds. Joshi et al. research provided more evidence [45], who discovered hesperidin as one of the numerous natural compounds that adhere to the primary protease of the SARS-CoV-2 virus. In addition, the viral receptor angiotensin-converting enzyme-2 is involved (ACE-2).

As a powerful antioxidant against superoxide and hydroxyl radicals, hesperidin plays an important role in antioxidant defense mechanisms [46], and hesperetin, a derivative of it, prevents LPS-stimulated microglial cells from producing nitric oxide [47]. Another research found that *Citrus* flavanones, such as naringenin and hesperidin, reversed age-related decreases in superoxide dismutase, catalase, and glutathione reductase in the livers of elderly rats [48]. Coronaviruses are one type of virus that causes the common cold, a condition for which there is no treatment or vaccination. Given the fact that SARS-CoV is a coronavirus, as well as the low cost and high security of fresh foods with high doses of vitamin C, it has been proposed that boosting regular consumption of these foods may be advantageous during the COVID-19 pandemic [49–51]. **Figure 3** shows hesperidin and L-ascorbic acid reduces the cell pattern of the SARS COVID-2 (SARS-CoV-2) infection, as well as the regions of infection, started cell, and fundamental illness (set apart with an "X") [37].

As well as aiding the development of collagen in connective tissue, L-ascorbic acid has antioxidant capacity, and when combined with other minerals, enzymes, and vitamins, can lessen the effects of free radicals. Human vascular smooth muscle cells are considered to be protected by vitamin C from apoptosis by preventing LDL oxidation [52]. *Citrus* fruits may have a substantial impact on COVID-19 therapy, through pathways other than viral replication suppression and antioxidant activity [37]. The numerous biological effects of vitamin C and hesperidin are two core aspects of *Citrus* fruits that appear to be excellent choices for counteracting SARS-CoV-2 cell infiltration and modulating the disease's systemic immuno-pathological stages. The more epidemiological, preclinical, and clinical study is required to verify the concept that a diet rich in *Citrus* fruits or comparable compounds may help COVID-19 prevention efforts [37].

#### **4.2 Antioxidant activity**

The primary source of reactive oxygen species (ROS) is oxygen, in living organisms through a variety of metabolic routes, such as hydroxyl radicals, hydrogen

**Figure 3.** *Hesperidin and vitamin C impact on infected cell cycle [37].*

peroxide, and superoxide anion, while antioxidant systems may combat them to maintain equilibrium [53]. However, contemporary lifestyle variables may increase the number of reactive oxygen species, which play an important role in the development of different diseases, such as inflammation, heart disease, arthritis, aging, and cancer, and produce oxidative stress. *Citrus* extracts, including *Citrus* bergamia juice extracts, karna peel extracts, and *Citrus limetta* peel extracts, have been demonstrated to have antioxidant activity [33, 34]. *Citrus* fruits are said to be high in antioxidants because they contain phenolic compounds with poly-hydroxyl groups, such as flavonoids, phenolic acids, and their derivatives [54]. The following are the major antioxidant mechanisms:

