Poster Presentation Australian Society for Microbiology Annual Scientific Meeting 2024

Antimicrobial peptides and their mimics can synergize to reduce the infection of Herpes simplex and Influenza viruses in cell culture (#107)

Mst Umme Laila Urmi 1 , Ajay Kumar Vijay 1 , Rajesh Kuppusamy 1 2 3 , Salequl Islam 1 4 , Naresh Kumar 2 , Mark Willcox 1
  1. School of Optometry and Vision Science, UNSW, Sydney, NSW, Australia
  2. School of Chemistry, UNSW, Sydney, NSW, Australia
  3. UNSW, Sydney, UNSW, NSW, Australia
  4. Department of Microbiology, Jahangirnagar University, Savar, Dhaka, Bangladesh

Herpes simplex virus (HSV-1) and influenza virus (e.g. H1N1) have significant global health concerns due to their potential for severe morbidity or mortality. While many antivirals have been made to combat viral infections, resistance is a growing problem. New therapeutics are needed, and combination therapy presents a promising approach to overcome the issue of resistance. In this study, we employed the checkerboard assay to assess the synergy between different antimicrobial peptides (AMPs) and their mimics against HSV-1 and H1N1. A fractional inhibitory concentration index (FICI) was calculated to evaluate the interaction between the compounds. The FICI was determined by summing the FICIs of both compounds. The FICI of each compound is determined by dividing the 50% inhibitory concentration (IC50) when combined with its IC50 when used alone. Synergy was indicated by an FICI ≤ 0.5; an additive effect by an FICI > 0.5 - ≤ 1.0; indifference by a FICI of > 1.0 - ≤ 4.0; and antagonism by an FICI > 4. Melimine, Mel4, and peptide mimics 610 and 758 were tested individually and in combination against HSV-1 and H1N1. When tested separately, mimic 610 exhibited IC50 values of 35µM against HSV-1 and 2.35µM against H1N1, while 758 showed IC50 values of 25µM against HSV-1 and 12.34µM against H1N1. However, neither peptide showed activity even at higher concentrations, such as 500µM. For HSV-1, Mel4 with 610 showed a synergy (FICI 0.375) while mimics 610 and 758 indicated an additive effect (FICI 0.75). When melimine was combined with 610, no inhibition was observed. However, using 610 with 758 showed synergy against H1N1 (FICI 0.5), while melimine and mel4 with 610 resulted in an additive effect (FICI 0.75 and 1, respectively). Although the FICI values suggest additive effects for some combinations, these compounds individually decreased their IC50 values significantly (at least a two-fold decrease), indicating promising combinations to reduce HSV-1 and H1N1 infection. The effective combinations of certain peptides and mimics show promise for new treatments against viruses. More studies are needed to understand how they work and make them even better at fighting viral infections.