The proposed efficacy is based on reported work up till now with correlation to disease progression. We aim to highlight the efficacy of Allium sativum against the COVID-19 through available scientific data.
Antiviral action and effect on ACE
Thiol enzymes have action on cysteine level which is less in COVID-19 Patients. The major chemical constituent of Allium sativum, Allicin acts by preventing several thiol enzymes; other constituents like ajone's have proven their efficacy in viral diseases through leukocytes prevention mechanism .
Some researchers revealed that the preventive action of Allium sativum against various viruses like influenza B, human rhinovirus type 2, human cytomegalovirus (HCMV), Parainfluenza virus type 3, herpes simplex type 1 and 2, vaccinia virus, and vesicular stomatitis virus .
Chemical constituents isolated from Allium sativum can inhibit adhesive interaction and fusion of leukocytes which leads by enhancement of natural killer cell (NK cell) activity which destroys the infected virus cells .
Many reviews suggested that allicin and S-allylcystein were found in Allium sativum inhibit the ACE receptor through the production of Hydrogen Sulfide (H2S) and stimulation of Nitric Oxide (NO), with blockage of α adrenergic receptors and calcium channels . Some studies suggested that extracts of Allium sativum can prevent from influenza A (H1N1) virus by inhibiting the nucleoprotein synthesis of virus and polymerase Activity .
Reduction of lung edema through inhibition of epithelial sodium channel
The epithelial sodium channel (ENaC) is an essential sodium selective ion channel that has three subunits, alpha, beta, and gamma. ENaCs expressed the rate-limiting step for the transepithelial absorption of sodium. The transport of sodium through the transepithelial generates osmotic gradients across epithelia, which as a result forces the osmotic transepithelial movement of water; Therefore ENaCs are key factors in the regulation of salt and water homeostasis in various organs .
The finding of ENaCs in the lungs are expressed in the airway epithelia which regulates the volume and composition of airway lining fluid and helps alveolar fluid clearance in the alveolar epithelium. In the lungs, increased ENaC activity in the airways can promote cystic fibrosis-like lung disease, whereas ENaC hypoactivity in the distal lung is associated with the formation of pulmonary edema .
The garlic compound allicin inhibits ENaC Characteristic through organosulfur compounds S-allyl-Lcysteine, alliin, allicin, and diallyl sulfides. Alliin is situated in the cytosol of garlic cells and which converted into allicin by the enzyme allinase. However, allinase is located in the vacuoles of the cells [15, 16].
Reduction of pro-inflammatory cytokines and chemokines
The pro-inflammatory cytokines and chemokines are produced by activated macrophages and they are said to be active on inflammation predominantly. In COVID-19 patients the major concern is hyperproduction of pro-inflammatory cytokines and chemokines which leads the disease progression .
Some researchers reported that allicin can decrease the level of pro-inflammatory cytokines on systemic and tissue levels. Allicin also modulates the production of IL-1ß, IL-6, and TNF-alpha at mRNA and different protein levels reported in in-vitro studies [18, 19, and 20].
Action on reactive oxygen species (ROS), inflammatory macrophage infiltration
The free radical scavenging is an essential function that takes care of our body through homeostasis. In a disease state, reactive species and macrophages play a vital role; the chemical constituents like allyl methyl sulfide and diallyl sulfide play a key role by inhibiting angiotensin-II-stimulated cell-cycle sequence, migration, and generation of reactive oxygen species (ROS) that indicates its efficacy in hypertension .
Allicin has the ability to break the lipid-soluble chain, which clearly explains its natural antioxidant property, concentration in the brain through crossing the blood–brain barrier, and accumulate at therapeutic levels in the brain. Allicin proved its efficacy by preventing reactive oxygen species damage by up-regulating enzymes that are involved in phase II detoxifying and by accelerating the cellular glutathione level .
Allicin may be efficacious due to its modulating property through the enzymatic activity of SH-containing enzymes by a thiol-disulfide exchange reaction. Some studies suggest that allicin has SH-modifying properties that show biological activity by inhibiting the LDL degradation which in turn shows its affinity to free thiol groups and blocks the LDL to macrophage receptors .
Allicin can be a good candidate drug for atherosclerosis and reduce plasma lipid concentrations and low-density lipoprotein receptor (LDLR), as it show the efficacy through modification and inhibition of LDL uptake, degradation by macrophages [24, 25].
Protects mitochondrial function
The mitochondrial functions are essential for the cells for energy-related functions. In COVID-19 Patients the mitochondrial damage causes platelet damage and apoptosis . Allicin inactivates the mitochondrial cytochrome, which is a major factor that activates multiple downstream signaling pathways in ischemic conditions to execute cell death .
In silico studies of allicin against coronavirus
Recent research based on in silico non-covalent and covalent docking screening methods implicates that allicin shows dual S-thioallylation of Cys-145 and solvent-exposed Cys-85/Cys-156 residue of SARS-CoV-2 Mpro which acts as a potent inhibitor of SARS-CoV-2 Mpro .