Plantaricin NC8 αβ rapidly and efficiently inhibits flaviviruses and SARS-CoV-2 by disrupting their envelopes
Abubakr A. M. Omer, Jorma Hinkula, Pham-Tue-Hung Tran, Wessam Melik, Elisa Zattarin, Daniel Aili, Robert Selegård, Torbjorn Bengtsson and Hazem Khalaf
Abstract:
Potent broad-spectrum antiviral agents are urgently needed to combat existing and emerging viral infections. This is particularly important considering that vaccine development is a costly and time-consuming process and that viruses constantly mutate and render vaccines ineffective. Antimicrobial peptides (AMPs), such as bacteriocins, are attractive candidates as antiviral agents against enveloped viruses. One of these bacteriocins is PLNC8 αβ, which consists of amphipathic peptides with positive net charges that display high affinity for negatively charged pathogen membrane structures, including phosphatidylserine-rich lipid membranes of viral envelopes. Due to the morphological and physiological differences between viral envelopes and host cell plasma membranes, PLNC8 αβ is thought to have a high safety profile by specifically targeting viral envelopes without affecting host cell membranes. In this study, we tested the antiviral effects of PLNC8 αβ against the flaviviruses Langat and Kunjin, coronavirus SARS-CoV-2, influenza A virus (IAV), and human immunodeficiency virus type 1 (HIV-1). The concentration of PLNC8 αβ required to eliminate all infective virus particles was in the nanomolar (nM) to micromolar (μM) range, which is surprisingly efficient considering the high cholesterol content (8–35%) of viral lipid envelopes. We found that viruses replicating in the endoplasmic reticulum (ER)/Golgi complex, such as SARS-CoV-2 and flaviviruses, were considerably more susceptible to PLNC8 αβ compared with viruses that acquire their lipid envelope from the plasma membrane, such as IAV and HIV-1. The development of novel broad-spectrum antiviral agents can significantly benefit human health by rapidly and efficiently eliminating infectious virions and thereby limiting virus dissemination and spread between individuals. PLNC8 αβ can potentially be developed into an effective and safe antiviral agent that targets the lipid compartments of viral envelopes of extracellular virions, largely independent of virus antigenic mutations that challenge many antiviral drugs and vaccines.