Air pollution particulate matter as a potential carrier of SARS-CoV-2 to the nervous system and/or neurological symptom enhancer: arguments in favor.

Entry receptor for SARS-CoV-2 is expressed in nasal epithelial cells, and nasal delivery pathway can be a key feature of transmission. Here, a possibility of interaction of SARS-CoV-2 with air pollution particulate matter (PM) was considered. It was shown in our recent studies that water-suspended plastic and wood smoke aerosol PM and carbon-containing nanoparticles from burning organics can interact with the plasma membrane of brain nerve terminals presumably due to their lipid components. COVID-19 patients have neurological symptoms, viral particles were found in the brain, SARS-CoV-2 enters the cells via fusion of lipid viral envelope with the plasma membranes of infected cells, and so viral envelop can contain lipid components of the host neuronal membranes. Therefore, interaction of SARS-CoV-2 envelope with PM is possible in water surrounding. After drying, PM can serve as a carrier for transmission of SARS-CoV-2 immobilized at their surface. Moreover, PM and SARS-CoV-2 per se can enter human organism during nasal inhalation, and they both use the same nose-to-brain delivery pathways moving along axons directly to the brain, influencing the nervous system and exocytosis/endocytosis in nerve cells. Thus, PM can aggravate neurological symptoms of SARS-CoV-2 and vice versa, due to their identical nose-to-brain delivery mechanism and possible interference of neuronal effects. In addition, different types of PM because of their ability to interact with the plasma membranes of nerve cells can facilitate unspecific SARS-CoV-2 entrance to the cells, and can influence envelope features of SARS-CoV-2. Detailed studies are required to analyze interaction of SARS-CoV-2 with PM.

Immunization with 674-685 fragment of SARS-Cov-2 spike protein induces neuroinflammation and impairs episodic memory of mice.

COVID-19 is accompanied by strong inflammatory reaction and is often followed by long-term cognitive disorders. The fragment 674-685 of SARS-Cov-2 spike protein was shown to interact with α7 nicotinic acetylcholine receptor involved in regulating both inflammatory reactions and cognitive functions. Here we show that mice immunized with the peptide corresponding to 674-685 fragment of SARS-Cov-2 spike protein conjugated to hemocyanin (KLH-674-685) demonstrate decreased level of α7 nicotinic acetylcholine receptors, increased levels of IL-1ß and TNFα in the brain and impairment of episodic memory. Choline injections prevented α7 nicotinic receptor decline and memory loss. Mice injected with immunoglobulins obtained from the blood of (KLH-674-685)-immunized mice also demonstrated episodic memory decline. These data allow suggesting that post-COVID memory impairment in humans is related to SARS-Cov-2 spike protein-specific immune reaction. The mechanisms of such effect are being discussed.

SARS-Cov-2 spike protein fragment 674-685 protects mitochondria from releasing cytochrome c in response to apoptogenic influence.

In spite of numerous studies, many details of SARS-Cov-2 interaction with human cells are still poorly understood. The 674-685 fragment of SARS-Cov-2 spike protein is homologous to the fragment of α-cobratoxin underlying its interaction with α7 nicotinic acetylcholine receptors (nAChRs). The interaction of 674-685 peptide with α7 nAChR has been predicted in silico. In the present paper we confirm this prediction experimentally and investigate the effect of SARS-Cov-2 spike protein peptide on mitochondria, which express α7 nAChRs to regulate apoptosis-related events. We demonstrate that SARS-Cov-2 spike protein peptide 674-685 competes with the antibody against 179-190 fragment of α7 nAChR subunit for the binding to α7-expressing cells and mitochondria and prevents the release of cytochrome c from isolated mitochondria in response to 0.5 mM H2O2 but does not protect intact U373 cells against apoptogenic effect of H2O2. Our data suggest that the α7 nAChR-binding portion of SARS-Cov-2 spike protein prevents mitochondria-driven apoptosis when the virus is uncoated inside the cell and, therefore, supports the infected cell viability before the virus replication cycle is complete.