VIP: A COVID-19 Therapeutic that Blocks Coronavirus Replication

Abstract

Vasoactive Intestinal Peptide has demonstrated an immediate clinical response in some patients with COVID-19 respiratory failure. A response of this magnitude has previously not been seen with an antiviral agent and is akin to the first reports of penicillin in treating pneumococcal pneumonia. Similar results have been demonstrated in acute respiratory distress syndrome caused by sepsis. Aviptadil, a synthetic form of human Vasoactive Intestinal Peptide (VIP) has been granted FDA Fast Track Designation and emergency IND authorization for the treatment of Critical COVID-19 with respiratory failure and is now in phase 2/3 clinical trials, with initial determinations of safety and non-futility. VIP binds uniquely to VPAC1 receptors on Alveolar Type II cells in the lung, the same cells that bind the SARS-CoV-2 virus via their ACE2 receptors. VIP protects those cells and the surrounding pulmonary epithelium by inhibiting replication of the SARS-CoV-2 virus, blocking cytokine synthesis, preventing apoptosis, and upregulating the production of surfactant, which is critical to pulmonary oxygenation. Because of its lack of toxicity and low cost of manufacture compared to proprietary biologics, VIP may be uniquely attractive to those focused on global countermeasures against COVID-19 and future threats.

Note: Funding: This work was supported by funding from Relief Therapeutics Holdings, AG, which owns intellectual property related to Aviptadil and by the Cavendish Impact Foundation.

Declaration of Interest: JCJ author is employed by NeuroRx, Inc., a pharmaceutical company that is currently conducting clinical trials of Aviptadil in patients with COVID-19 and has a financial interest in the outcome of those clinical trials. All scientific publications cited are published by authors with no known financial interest.

Keywords: VIP, Aviptadil, COVID-19, coronavirus, SARS-CoV-2, viral replication, cytokine, surfactant, calu-3