Abstract
Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) has caused worldwide panic during 2020. To date SARS-CoV-2, the virus causing COVID-19, has caused 1 million deaths and infected over 35 million people in under 10 months. On the other hand, influenza A virus (IAV) has been responsible for several epidemics and millions of deaths during the last 100 years. Our study joins the race to identify novel COVID-19 treatments by investigating the antiviral capabilities and clinical potential of a series of antimicrobial peptides and peptoids against these two important respiratory viruses. The project aimed to identify potential candidates within a panel of peptides (n=4) and peptoids (n=14) kindly provided by Dr. Daniel Pletzer (University of Otago, New Zealand) and A/Prof Annelise Barron (Stanford University, USA), respectively. Standard drug discovery strategies were employed to determine the ability of the peptides/peptoids to inhibit viral replication (EC50 values), while causing negligible cytotoxicity (CC50 values) in different cell lines. We uncovered 8 peptides/peptoids which showed antiviral activity against IAV (EC50 values ranging from 49 μg/ml to 5.7 ug/ml), as well as 12 antimicrobial peptides/peptoids able to inhibit the replication of SARS-CoV-2 (EC50 values range, 41 μg/ml to 3.2 ug/ml). In summary, promising selectivity index (SI) values warrant continued characterization of the antiviral activity of the novel antimicrobial peptides/peptoids, including but not limited to (i) verifying their specificity by testing other influenza and coronavirus strains and (ii) in vitro selection of viruses with reduced susceptibility to these peptides/peptoids. Our results add to the growing evidence that some antimicrobial peptides and peptoids are also capable of inhibiting viral replication. The need for additional SARS-CoV-2 and IAV treatments is urgent and studies such as this one contribute to essential research against these deadly viruses.