RT Journal Article SR Electronic T1 Varenicline Prevents SARS-CoV-2 Infection In Vitro and in Rhesus Macaques JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.06.29.450426 DO 10.1101/2021.06.29.450426 A1 Jeffrey Nau A1 Priya Luthra A1 Kathleen Lanzer A1 Frank Szaba A1 Tres Cookenham A1 Eric Carlson YR 2021 UL http://biorxiv.org/content/early/2021/06/30/2021.06.29.450426.abstract AB Background SARS-CoV-2 infections have resulted in a global pandemic, but an antiviral therapy for this novel strain of coronavirus does not currently exist. The objective of our study was to investigate the antiviral potential of the nicotinic acetylcholine receptor (nACHR) agonist varenicline tartrate against SARS-CoV-2.Methods We assessed antiviral activity using in vitro human cell assays and we assessed in vivo efficacy in a rhesus macaque model.Results In vitro studies found that varenicline tartrate, over a range of concentrations, reduced the infectivity of SARS-CoV-2 wildtype, alpha, and beta variants in Calu-3 cells and Caco-2 cells, with maintenance of cell viability. In vivo studies found that varenicline tartrate, administered as a nasal spray to rhesus macaques, reduced SARS-CoV-2 wildtype viral load and inhibited viral replication in the nasal mucosa and upper airway.Conclusion Although the study reported here was exploratory, we have confirmed that the nAChR agonist varenicline has the potential to interact with and inhibit SARS-CoV-2 infection and replication.Competing Interest StatementThe authors have declared no competing interest.