Gramicidin S and melittin: potential anti-viral therapeutic peptides to treat SARS-CoV-2 infection

Abstract

The COVID19 pandemic has led to multipronged approaches for treatment of the disease. Since de novo discovery of drugs is time consuming, repurposing of molecules is now considered as one of the alternative strategies to treat COVID19. Antibacterial peptides are being recognized as attractive candidates for repurposing to treat viral infections. In this study, we describe the anti-SARS-CoV-2 activity of the well-studied antibacterial peptides gramicidin S and melittin obtained from Bacillus brevis and bee venom respectively. The EC50 values for gramicidin S and melittin were 1.571 µg and 0.656 µg respectively based on in vitro antiviral assay. Significant decrease in the viral load as compared to the untreated group with no/very less cytotoxicity was observed. Both the peptides treated to the SARS-CoV-2 infected Vero cells showed viral clearance from 12 h onwards with a maximal viral clearance after 24 h post infection. Proteomics analysis indicated that more than 250 proteins were differentially regulated in the gramicidin S and melittin treated SARS-CoV-2 infected Vero cells against control SARS-CoV-2 infected Vero cells after 24 and 48 h post infection. The identified proteins were found to be associated in the metabolic and mRNA processing of the Vero cells post-treatment and infection. Both these peptides could be attractive candidates for repurposing to treat SARS-CoV-2 infection.

Genomewide Analysis and Biological Characterization of Cathelicidins with Potent Antimicrobial Activity and Low Cytotoxicity from Three Bat Species

“…Endogenous AMPs also showed antiviral activity against diverse viruses, including the human influenza virus, human immunodeficiency virus, rabies virus, West Nile virus (WNV), and herpes simplex virus (HSV) [ 25 , 67 , 68 , 69 , 70 ]. Among them, gramicidin S and melittin from Bacillus brevis and bee venom, respectively, showed noteworthy anti-SARS-CoV-2 effects with viral particle reduction compared to remdesivir, a repurposed drug used to treat the infection [ 71 ]. Antiviral activities against HSV and WNV were also reported for other cathelicidins, such as LL-37, Pb-CATH4, Hg-CATH, and ModoCath5 [ 25 , 70 , 72 ].…”

A proteomic perspective and involvement of cytokines in SARS-CoV-2 infection

“…After brief centrifugation, the supernatant was collected and quantified using the amido black method [36]. A total of 200ug of protein was in-gel trypsin digested and labelled with iTRAQ label as per previously mentioned protocol [36][37][38][39][40]. SARS-COV-2 negative samples were labelled with iTRAQ 114 and 115, and positive samples were labelled with 116 and 117.…”

Harnessing the Power of Venomous Animal-Derived Toxins against COVID-19

“…Authors hypothesized that the whole venom may attenuate the cytokine storm caused by SARS-CoV-2 and could be used in a prophylactic context for COVID-19 [ 71 , 72 ]; in addition, melittin was tested for in vitro assay using Vero cells and it was found that it could neutralize SARS-CoV-2 virus, showing more pronounced antiviral activity at 12 h with 95% of viral reduction; also, the effect of melittin on the ability of the virus to infect Vero cells was studied through high-throughput proteomic analysis. The omics analysis revealed that proteins were found to be down-regulated in the cells following melittin treatment, indicating that the toxin induces a metabolic effect and not merely viral lysis [ 73 ]. Although this study shows benefits of melittin against SARS-CoV-2, a formulation containing melittin must be very well adjusted so that it causes no cytolytic effects [ 73 , 74 ].…”

“…The omics analysis revealed that proteins were found to be down-regulated in the cells following melittin treatment, indicating that the toxin induces a metabolic effect and not merely viral lysis [ 73 ]. Although this study shows benefits of melittin against SARS-CoV-2, a formulation containing melittin must be very well adjusted so that it causes no cytolytic effects [ 73 , 74 ].…”