The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly pathogenic and transmissible virus that caused nearly one billion infections and over seven million deaths worldwide, along with devastating effects on economies and health systems. A diverse array of treatments has been evaluated, ranging from conventional measures such as oxygen therapy and corticosteroids to antiviral agents targeted therapies, and vaccines. No singular option has emerged as a universally approved remedy for COVID-19.
Mecamylamine, a nicotinic receptor antagonist, can block nAChRs, preventing virus binding and decreasing viral replication and cytokine expression. By binding to α and β subunits of nAChRs, mecamylamine prevents the virus from interacting with these receptors, inhibiting replication and reducing overall viral load. During viral infections like MHV4, excessive cytokine production can cause severe inflammation and tissue damage. Mecamylamine decreases the expression of pro-inflammatory cytokines and regulates cytokine production. Additionally, mecamylamine inhibits the transmission of nerve impulses in the sympathetic nervous system, leading to lowered blood pressure, and helps mitigate CNS-related COVID-19 symptoms such as headache, nausea, and vomiting.
PG -Mecamylamine treatment reduces the SARS-CoV-2 replication. Calu3 cells were infected with 0.1 MOI SARS CoV2 and treated with Pioglitazone (PG, 20uM) and/ or Mecamylamine ( Mec, 5uM) or Mecamylamine isomer (Mec iso, 5uM) for 48 hrs. Post 48 hrs the infection the cells were collected in Trizol and RNA was extracted for PCR analysis. The histogram presents the fold change of SARS CoV2 N protein expression, n = 3, Data expressed as mean ± SEM, Mock- UV inactivated, # compared to Mock,* compared to control, *p<0.05,**p<0.005,### ,***p<0.0005.