**13. Vitamin B9 (folic acid, folate) as furin inhibitor**

For DNA, synthesis of protein and adaptive immune reaction, folate seems to be essential vitamin. Furin is a bacterial and viral infections-related enzyme and a good potential goal for infection treatment. Folic acid has recently been noted for being capable of inhibiting furin by avoiding binding of the spike protein SARS-CoV-2 and trying to prevent cell input and virus retention. Follic acid was thus recommended to be helpful for COVID-19-associated early phase respiratory disease management [44]. A latest publication shows the strength and stability of folic acid and its derivatives tetrahydrofolic acid and 5 methyl tetrahydrofolic acid, via structure-based molecular docking, in connection with SARS-CoV-2. Follic acid can thus be used as a treatment strategy for COVID-19 management [45].

#### **14. Vitamin B12 (cobalmin) as antioxidant and gut modulatory agent**

For the synthesis of erythrocytes, safety of the nervous system, myelin production, angiogenesis and rapid production of DNA, vitamin B12 is critical. Adenosyl-, h ydroxo- and methyl cobalamin are active forms of vitamin B12. As modulator for intestinal flora and low B12 concentrations, vitamin B12 increases homocysteine

#### **Figure 2.**

*Summary of Vitamin B complex as anti-COVID-19 agent for inhibition of viral replication, viral binding and invasion, cytokine storm and hypercoagulabity [9].*

and methyl malonic acid, leading to increasing inflammatory process, ROS and oxidative stress [35]. Reduced immune response, endothelial dysfunction, myelin sheathing integrity interruption, megaloblastic anaemia, platelets and coagulation activation and are caused by hyperhomocysteinemia [46–48]. SARS-CoV-2 may perhaps interact with the metabolic activities of vitamin B12 which may affect microbiological bowel propagation. Provided that symptoms such as vasoconstriction, increased oxidative stress, cascade-activation of clotting, lactate dehydrogenase, renal and pulmonary vascular disorder and hyperhomocysteinemia are feasible [47, 49]. Furthermore, B12 insufficiency can lead to CNS, gastrointestinal and respiratory and abnormalities [48]. Remarkably, a new study shows that additional methylcobalamine may minimise damage to the organs and symptoms associated with COVID 19 [50]. A Singapore diagnostic research demonstrates that the intensity of COVID-19 in patients receiving magnesium, vitamin D (1000 IU) and vitamin B12 supplements (500 μg), reduced considerably the need for COVID-19 symptoms [51]. **Figure 2** shows a summary of the anti-viral vitamin B complex.
