The Intestinal Perspective of COVID-19: NOS2 and AOC1 Genes as Epidemiological Factors, and a Homeopathic Approach to their Functional Improvement

Abstract

AbstractThe new pandemic disease COVID-19 has wreaked havoc worldwide. Its infectious agent, SARS-CoV-2, uses two key human enzymes called angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) to invade body cells. The first one is encoded by the ACE2 gene and the second by the TMPRSS2 gene. Both have an outstanding expression of RNA and proteins in the small intestine compared with other tissues. This prominent location may be related to the main entry route of SARS-CoV-2 into the organism. In the process of infection, two other genes can play a fundamental role: NOS2, which expresses inducible nitric oxide synthase (iNOS), and AOC1, which encodes diamine oxidase (DAO). Both also highlight in the small intestine and are involved in polyamine metabolism. These biogenic amines are important for viral replication, being enhanced when NOS2 and AOC1 genes are downregulated. In addition, NOS2 shows a negative correlation with ACE2 and TMPRSS2, while nondegraded histamine by DAO can lead to an upregulation of both genes on which the virus depends. Taken together, these data suggest that inhibition or underexpression of NOS2 and AOC1 determines the susceptibility to get sick, increasing the risk of infection. On the other hand, a therapeutic approach to the disease could be made with homeopathic medicines. Experiments show the remedies' ability to stimulate gene and protein expression, but a correlation between the symptoms of each drug and these expressions has not yet been established. Here an analysis of the pathogenesis of Silicea terra and Arsenicum album supported on the scientific literature is done. The objective is to propose a theory about their relationship with key genes whose protein expressed in deficiency can give rise to the chain of events that imbalance the internal environment (homeostasis) and allow the development of symptoms. Silicea seems to be related to NOS2 (gene)/iNOS (protein) and Arsenicum with AOC1 (gene)/DAO (protein), being necessary to carry out studies to corroborate these links. Therefore, the aim of this article is to show the importance of NOS2 and AOC1 genes in the development of COVID-19 and to propose a line of investigation to evaluate if homeopathy can improve their protein expression.