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Principal Investigator: PEI TANG
Organization: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
Fiscal Year: 2020
Award: $156,491
Funding agency: National Institute on Drug Abuse
The alpha7 nicotinic acetylcholine receptor (α7nAChR) has emerged as a unique player in the infection and
progression of COVID-19, which has caused more than 325,000 deaths. α7nAChR links tobacco smoking to
major clinical manifestations in COVID-19, including respiratory infection, anosmia, systemic coagulopathy, and
cytokine storm. Several sequences of SARS-CoV-2 are found to be homologous to α-bungarotoxin and α-
cobratoxin, potent antagonists of α7nAChR. These findings support the hypothesis that SARS-CoV-2 interacts
directly with α7nAChR, inhibits its function, and consequently dysregulates the inflammatory responses mediated
by α7nAChR. The experimental evidence is urgently needed to correctly establish the role of α7nAChR in
COVID-19 and to understand nicotine’s detrimental or protective effects on the onset and progression of COVID-
19. With permission from the NIDA (Dr. Roger Little, Deputy Director, Division of Neuroscience and Behavior),
we seek Administrative Supplement support to address several key questions about the involvement of nicotine
and α7nAChR in COVID-19. Specifically, we propose to elucidate: (1) where and how SARS-CoV-2 proteins
interact with α7nAChR and how nicotine alters such interactions; and (2) how SARS-CoV-2 proteins affect
intracellular signaling pathways downstream of α7nAChR that lead to upregulation and transactivation of pro-
inflammatory cytokines, and how nicotine modulates the outcome of this process. Considering the widespread
expression of α7nAChR in various organs and the significant regulatory role of α7nAChR in the cholinergic anti-
inflammatory pathway, our research outcomes can potentially lead to new treatment strategies to combat
COVID-19.
Terms: <2019 novel coronavirus><2019-nCoV><Address><Administrative Supplement><Affect><Agonist><Angiotensin Converting Enzyme><Angiotensin I-Converting Enzyme><Animal Model><Animal Models and Related Studies><Anosmia><Anti-Cholinergics><Anti-Inflammatories><Anti-Inflammatory Agents><Anti-inflammatory><Anticholinergic Agents><Anticholinergics><Antiinflammatories><Antiinflammatory Agents><Authorization><Authorization documentation><Behavior><Binding><Blood Coagulation Disorders><CD143 Antigens><COVID-19><COVID-19 epidemic><COVID-19 pandemic><COVID19><COVID19 epidemic><COVID19 pandemic><Carboxycathepsin><Cell Body><Cell Communication and Signaling><Cell Signaling><Cell model><Cells><Cellular model><Cessation of life><Clinical><Coagulation Disorder><Coagulopathy><Coupling><Death><Dipeptidyl Peptidase A><Disease><Disorder><Electrophysiology><Electrophysiology (science)><Environment><Exposure to><Foundations><Funding><Goals><Human><Infection><Inflammation><Inflammatory><Inflammatory Response><Intracellular Communication and Signaling><Kininase A><Kininase II><Knowledge><Lead><Length><Link><Measures><Mediating><Modern Man><Molecular><Molecular Interaction><NIDA><NMR Spectrometer><NMR Spectroscopy><National Institute of Drug Abuse><National Institute on Drug Abuse><Neurophysiology / Electrophysiology><Neurosciences><Neurotoxins><Nicotine><Nicotinic Acetylcholine Receptors><Nicotinic Receptors><Organ><Outcome><Outcomes Research><Pathway interactions><Patients><Pb element><Peptidyl-Dipeptidase A><Permission><Play><Position><Positioning Attribute><Process><Production><Prognosis><Protein C><Proteins><Receptor Protein><Research><Research Resources><Resources><Respiratory Infections><Respiratory Tract Infections><Role><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Sequence Homology><Severe acute respiratory syndrome coronavirus 2><Signal Pathway><Signal Transduction><Signal Transduction Systems><Signaling><Snake Venoms><Structure><Surface Plasmon Resonance><Testing><Therapeutic Effect><Tobacco smoking><Tobacco smoking behavior><Transactivation><Transfection><Up-Regulation><Upregulation><Viral Diseases><Virus Diseases><Wuhan coronavirus><alpha Bungarotoxin><alpha-bungarotoxin binding sites><alpha-bungarotoxin receptor><alpha7 nicotinic acetylcholine receptor><alpha7nAChR><anosphrasia><antiinflammatory><base><biological signal transduction><bleeding disorder><clotting disorder><combat><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease 2019><coronavirus disease 2019 epidemic><coronavirus disease 2019 pandemic><cytokine><cytokine release syndrome><cytokine storm><design><designing><effective therapy><effective treatment><electrophysiological><experience><extracellular><heavy metal Pb><heavy metal lead><macrophage><model of animal><model organism><neurotoxicant><neurotropic><nuclear magnetic resonance spectroscopy><outcome forecast><pathway><prevent><preventing><protective effect><receptor><response><social role><trans-activation><treatment strategy><viral infection><virus infection><virus-induced disease><α-Bungarotoxin><α7 nicotinic acetylcholine receptor><α7nAChR>