Protective effects of VIP and PACAP in SARS-CoV-2 infection

Temerozo, Jairo R.; Sacramento, Carolina Q.; Fintelman-Rodrigues, Natalia; Pão, Camila R. R.; de Freitas, Caroline S.; da Silva Gomes Dias, Suelen; Ferreira, André C.; Mattos, Mayara; Soares, Vinicius Cardoso; Teixeira, Lívia; de Azevedo-Quintanilha, Isaclaudia G.; Hottz, Eugenio D.; Kurtz, Pedro; Bozza, Fernando A.; Bozza, Patrícia T.; Souza, Thiago Moreno L.; Bou-Habib, Dumith Chequer

Infection by SARS-CoV-2 may elicit uncontrolled and damaging inflammatory response, thus it is critical to identify compounds able to inhibit virus replication and thwart the inflammatory reaction. Here, we show that the immunoregulatory neuropeptides VIP and PACAP were able to inhibit SARS-CoV-2 RNA synthesis in human monocytes and viral production in lung epithelial cells, protect the cells from virus-induced cytopathicity and reduce the production of proinflammatory mediators. Both neuropeptides prevented the SARS-CoV-2-induced activation of NF-kB and SREBP1 and SREBP2, transcriptions factors involved in proinflammatory reactions and lipid metabolism, respectively, and promoted CREB activation in infected monocytes, a transcription factor with antiapoptotic activity and also a negative regulator of NF-kB. VIP levels were elevated in plasma from patients with severe COVID-19, which correlated with the inflammatory marker CRP, viral load, and survival on those patients. Our results provide scientific evidence to further support clinical investigation of these neuropeptides against COVID-19.