Alpha-1 Antitrypsin for COVID-19 Treatment: Dual Role in Antiviral Infection and Anti-Inflammation.

Chengliang Yang,Mingyao Liu,Shaf Keshavjee

doi:10.3389/fphar.2020.615398

Abstract

Many drugs have been approved for clinical trials for the treatment of COVID-19 disease, focusing on either antiviral or anti-inflammatory approaches. Combining antiviral and anti-inflammatory drugs or therapies together may be more effective. Human alpha-1 antitrypsin (A1AT) is a blood circulating glycoprotein that is best known as a protease inhibitor. It has been used to treat emphysema patients with A1AT deficiency for decades. We and others have demonstrated its role in reducing acute lung injury by inhibiting inflammation, cell death, coagulation, and neutrophil elastase activation. Recently, A1AT has been found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by inhibiting transmembrane serine protease 2 (TMPRSS2), a protease involved in the entry of SARS-CoV-2 into host cells. This dual role of both antiviral infection and anti-inflammation makes A1AT a unique and excellent candidate for COVID-19 treatment. Three clinical trials of A1AT for COVID-19 treatment have recently been approved in several countries. It is important to determine whether A1AT can prevent the progress from moderate to severe lung injury and eventually to be used to treat COVID-19 patients with acute respiratory distress syndrome.

Highlights

The coronavirus disease 2019 (COVID-19) pandemic has caused a surge of critically ill patients in intensive care units across the world
It has been estimated that 1.7 billion people have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (Clark et al, 2020)
Using a pig-lung transplant survival model, we demonstrated the beneficial effects of alpha-1 antitrypsin (A1AT) on animal recovery via the lung transplant procedure

Summary

INTRODUCTION

The coronavirus disease 2019 (COVID-19) pandemic has caused a surge of critically ill patients in intensive care units across the world. It has been estimated that 1.7 billion people have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (Clark et al, 2020). The underlying mechanisms of COVID-19 are severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection-induced inflammatory response, cell death, microthrombus formation, and formation of neutrophil extracellular traps (NETs) (Middleton et al, 2020). Many clinical trials have been focused on drugs that have either antiviral infection or anti-inflammatory function. It has been suggested that a combination of anti-inflammatory drugs with direct-acting antivirals could reduce viral infectivity, viral replication, and the aberrant host inflammatory response (Stebbing et al, 2020). Drugs with a dual role in both anti-inflammation and antiviral infection could be excellent candidates for COVID-19 treatment

FDA approval

Usual care plus placebo Intravenous infusion

Findings

RESEARCH AGENDA