Systems Bioinformatics Reveals Possible Relationship between COVID-19 and the Development of Neurological Diseases and Neuropsychiatric Disorders.

Coronavirus Disease 2019 (COVID-19) is associated with increased incidence of neurological diseases and neuropsychiatric disorders after infection, but how it contributes to their development remains under investigation. Here, we investigate the possible relationship between COVID-19 and the development of ten neurological disorders and three neuropsychiatric disorders by exploring two pathological mechanisms: (i) dysregulation of host biological processes via virus-host protein-protein interactions (PPIs), and (ii) autoreactivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epitopes with host "self" proteins via molecular mimicry. We also identify potential genetic risk factors which in combination with SARS-CoV-2 infection might lead to disease development. Our analysis indicated that neurodegenerative diseases (NDs) have a higher number of disease-associated biological processes that can be modulated by SARS-CoV-2 via virus-host PPIs than neuropsychiatric disorders. The sequence similarity analysis indicated the presence of several matching 5-mer and/or 6-mer linear motifs between SARS-CoV-2 epitopes with autoreactive epitopes found in Alzheimer's Disease (AD), Parkinson's Disease (PD), Myasthenia Gravis (MG) and Multiple Sclerosis (MS). The results include autoreactive epitopes that recognize amyloid-beta precursor protein (APP), microtubule-associated protein tau (MAPT), acetylcholine receptors, glial fibrillary acidic protein (GFAP), neurofilament light polypeptide (NfL) and major myelin proteins. Altogether, our results suggest that there might be an increased risk for the development of NDs after COVID-19 both via autoreactivity and virus-host PPIs.

A Computational Approach Identified Andrographolide as a Potential Drug for Suppressing COVID-19-Induced Cytokine Storm.

BACKGROUND: The newly identified betacoronavirus SARS-CoV-2 is the causative pathogen of the coronavirus disease of 2019 (COVID-19) that killed more than 3.5 million people till now. The cytokine storm induced in severe COVID-19 patients causes hyper-inflammation, is the primary reason for respiratory and multi-organ failure and fatality. This work uses a rational computational strategy to identify the existing drug molecules to target host pathways to reduce the cytokine storm. RESULTS: We used a "host response signature network" consist of 36 genes induced by SARS-CoV-2 infection and associated with cytokine storm. In order to attenuate the cytokine storm, potential drug molecules were searched against "host response signature network". Our study identified that drug molecule andrographolide, naturally present in a medicinal plant Andrographis paniculata, has the potential to bind with crucial proteins to block the TNF-induced NFkB1 signaling pathway responsible for cytokine storm in COVID-19 patients. The molecular docking method showed the binding of andrographolide with TNF and covalent binding with NFkB1 proteins of the TNF signaling pathway. CONCLUSION: We used a rational computational approach to repurpose existing drugs targeting host immunomodulating pathways. Our study suggests that andrographolide could bind with TNF and NFkB1 proteins, block TNF-induced cytokine storm in COVID-19 patients, and warrant further experimental validation.