Hydroxychloroquine (1) was first announced as drug which can work on COVID19 and USFDA initially approved it as emergency medicine in the fight against COVID19 as the first available therapy, which was later scrutinized by USFDA while using in heart patients (2,3). Hydroxychloroquine was administered in patients from China with COVID19 RNA positive by RTPCR and above 12 years of age (4). Existing health issues i.e. Cardiovascular Vascular Disease (CVD) and Type 2 Diabetes (T2D) are more prone to COVID19 pathogenesis along with immunocompromised host, cancers and very recently as per WHO, cigarett smokers too (5).
Virus enter in the host cell by receptor mediated endocytosis i.e. its spike protein acts as a ligand and Angiotensin-converting enzyme 2 (ACE2) as a receptor (6). ACE2 receptors are more expressed due to ACE1 inhibitors and other ACE Receptors Blockers (ARB) (7). In presence of Coronavirus Pandemic, drugs which are being used for treatment of CVD and T2D needs to be reviewed because it helps to express more ACE2 receptors...(inhibitors of ACE1 induces expression of more ACE2 receptors). More ACE2 receptors....more enhanced Coronavirus infection and faster pathogensis...wherever ACE2 receptors express i.e. epithelial cells of the in lung, small intestine, kidney and blood vessels.
For type 2 diabetes, additionally threashold Zn levels should be maintained. Metal deficiency is well known in type 2 diabetes. We conducted metal deficiency studies in Indian type 2 diabetes patients. Although Chromium was below detection levels and Zinc data was not significant, Magnesium data we reported successfully in Indian type 2 diabetes in 2006 and we reported that Mg deficiency is there in Indian T2D patients (7). However, few studies reported Zinc depletion in type 2 diabetes. Pancreatic Beta cells are supplied with highest concentration of Zinc in normal individuals (8). Excessive urination depletes Zn (9).
In the context of Coronavirus treatment, HydroxyChloroquine acts as ionophore for Zn (8). Zinc is believed to be inhibiting various enzyme activities of RNA viruses (9), Multiple antivirual effects of Zinc have been demonstrated in a variety of viruses including Nidoviruses , where SARS CoV-2 virus belongs. It is suggested that Zn supplementation may be beneficial in the prophylaxis and the treatment of SARS Coronavirus 2 (10). Most crucial is the enzyme activity of RdRp (RNA dependent RNA polymerase i.e. RdRp, viral non structrural enzyme which replicates viral genome in the infected cells), More studies are needed to find out actual mechanism using the SARS Coronavirus 2 strain for such studies. Additionally, other than gating function for Zn, Chloroquine also works in the virus maturation stage i.e. glycosylation of viral protein i.e. viral surface glycoproteins.
As one suit not fit to all, Coronavirus therapeutics needs to be seen in different perspectives. It minght be the fact that, all therapeutics are not fit for all patients and age groups.
Whether Zinc deficiency in type 2 diabetes, affects chloroquine treatment in type 2 diabetes ? Additionally, whether type 2 diabetes should be given moderately high dosages of Zn ? along with Vitamin C. High Vitamin C level keeps heart healthy. Reduced level of Vitamin C hardens arteries, that's well known...So, for cardiovascular disease and type 2 diabetes..
Combination of Vitamin C and Zinc can be advised as supplements even if there is no Coronavirus infection. So that, if viral attacks, sufficient levels of Vitamin C and Zn will be helpful in Hydroxy Chloroquine therapy at later stage.
Dr. Devendra Lingojwar
Author is involved in various COVID19 related consultancy services since Emergence of COVID19 Pandemic. He provides consultancy services for Lab diagnostics, Antiviral testing against model strains of Coronaviruses, Animal toxicity studies including skin allergies and inhalation toxicity, COVID19 Viral Real Time PCR based testing services with different laboratories in India. His company also provides Lab design (BSL2, BSLl2+ and BSL3), skill development in Molecular Biology including PCR, RT PCR, Genomics, Import and Export of Pharma and Biopharma products and raw material supply in Western countries to various Government and non Government agencies, Private National and International companies, with panel of virologists located around the World.