Biological and Medicinal Chemistry

COVID-19: ORF8 Synthesizes Nitric Oxide to Break the Blood-Brain/Testi Barrier and Damage the Reproductive System

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Abstract

Studies have reveal that the SARS-CoV-2 virus can break through the blood-brain/testi barrier and invade the human reproductive system, causing infertility or complications in patients. Excessive nitric oxide (NO) is a fundamental reason for breaking the Blood-Brain/Testi Barrier. Nitric oxide often relates the spread or replication of many viruses in the body. The nitric oxide synthase (NOS) that synthesizes NO in the human by binding heme to complete the oxygenase reaction. This study focused on the relationship between heme, NO, and the novel coronavirus using bioinformatics methods such as domain search and molecular docking. The results showed ORF8 had three domains similar to nitric oxide synthase : oxygenase, reductase, and calmodulin (CaM). ORF6 could bind to these three domains. The dimer of ORF8 was identical to the dimer of NOS enzyme. The oxygenase domain was in the core, and the reductase domain was on both sides. ORF8 could capture Heme, H4B, L-arginine, FAD, FMN, and NADPH, and bind with CaM protein to catalyze NO production. The heme bound by ORF8 mainly came from the attacked hemoglobin. ORF8 also attached to E protein and synthesized NO through the heme hunted by E protein. We believed NO synthesized by ORF8 inhibited SARS-CoV-2 from reinfecting infected cells and controlled the virus replication speed to avoid cell collapse because of exhaustion of resources. After the SARS-CoV-2 virus combined with an extensive ORF8, the produced NO stream permeably expanded blood vessels and broke the blood-brain/testi barrier. The SARS-CoV-2 virus spread to nearby tissues through small blood vessel holes created by NO stream. It would increase the tendency to bleed and the blood clotting of the tissue: blood clotting and viral infections severely damaged organs such as the respiratory, heart, nerve, reproductive. Short NO could not open vascular permeability dilation, causing high viral load in asymptomatic patients' blood. Excessive NO stimulated the reproductive organs and generated abnormal functions. It also made abnormal hormone regulation, such as excessive secretion of luteinizing hormone (LH). Much LH would hurt the reproductive organs, leading to infertility. Extreme NO also interfered with the human NO signaling pathway and damaged the immune nerve, metabolism, cardiovascular and other systems. This theory is for academic discussion only. We hope that this discovery will help block the virus’s transmission through the human circulatory system and help reproductive health management during the pandemic.

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