Brilacidin tetrahydrochloride (PMX-30063) is a synthetic, nonpeptidic, small-molecule mimetic of Host Defense Proteins/Peptides (HDPs). It exhibits broad-spectrum inhibitory activity in bacteria and viruses, and also has immunomodulatory capabilities and anti-inflammatory properties [1-3].
Brilacidin tetrahydrochloride, when used at concentrations of 10-20 µM for 24 hours, demonstrates strong ability to inhibit SARS-CoV-2 in a human lung cell line that expresses ACE2 (Calu-3 cells) [4]. Brilacidin tetrahydrochloride (50µg/ ml;24h) inhibits replication-competent SARS-CoV-2 virus infection when added before viral entry [5]. The combination of Brilacidin (40 µM; 24h) + ibrexafungerp is not toxic and reduces the A. fumigatus fungal burden during the infection of A549 lung epithelial cells[6].
Combining Brilacidin tetrahydrochloride with caspofungin (CAS) effectively eliminates A. fumigatus lung infection in an immunosuppressed murine model of invasive pulmonary aspergillosis. Additionally, Brilacidin tetrahydrochloride alone (administered at 5 uL, 2.5 mM concentration, repeated 16 times over 3 days) reduces A. fumigatus fungal load and prevents disease progression in a murine model of fungal keratitis [6].
References:
[1]. Tew GN, Liu D, et,al. De novo design of biomimetic antimicrobial polymers. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5110-4. doi: 10.1073/pnas.082046199. PMID: 11959961; PMCID: PMC122730.
[2]. Brilacidin as a Successful Example of de Novo Drug Design; Innovation Pharmaceuticals: Wakefield, MA, USA, 2017.
[3]. Mensa B, Howell GL, et,al. Comparative mechanistic studies of brilacidin, daptomycin, and the antimicrobial peptide LL16. Antimicrob Agents Chemother. 2014 Sep;58(9):5136-45. doi: 10.1128/AAC.02955-14. Epub 2014 Jun 16. PMID: 24936592; PMCID: PMC4135847.
[4]. Bakovic A, Risner K, et,al. Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture. Viruses. 2021 Feb 9;13(2):271. doi: 10.3390/v13020271. PMID: 33572467; PMCID: PMC7916214.
[5]. Xu C, Wang A, et,al. Brilacidin, a Non-Peptide Defensin-Mimetic Molecule, Inhibits SARS-CoV-2 Infection by Blocking Viral Entry. EC Microbiol. 2022 Apr;18(4):1-12. Epub 2022 Mar 8. PMID: 35695877; PMCID: PMC9186380.
[6]. Dos Reis TF, Diehl C, et,al. Brilacidin, a host defense peptide mimetic, potentiates ibrexafungerp antifungal activity against the human pathogenic fungus Aspergillus fumigatus. bioRxiv [Preprint]. 2024 Apr 5:2024.04.05.588305. doi: 10.1101/2024.04.05.588305. PMID: 38617338; PMCID: PMC11014541.
[7]. Dos Reis TF, de Castro PA, et,al. A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi. Nat Commun. 2023 Apr 12;14(1):2052. doi: 10.1038/s41467-023-37573-y. PMID: 37045836; PMCID: PMC10090755.
Brilacidin tetrahydrochloride (PMX-30063)是一种合成的、非肽的、小分子的宿主防御蛋白/肽(HDP)模拟物。它对细菌和病毒具有广谱抑制活性,并具有免疫调节能力和抗炎特性[1-3]。
Brilacidin tetrahydrochloride (10-20 µM;2+24h)在ACE2-positive的人肺细胞系(Calu-3细胞)中显示出对SARS-CoV-2的有效抑制[4]。在病毒进入前加入Brilacidin tetrahydrochloride (50µg/ ml;24h)可抑制复制能力强的SARS-CoV-2病毒感染[5]。Brilacidin tetrahydrochloride (40 µM; 24h) + ibrexafungerp联合使用无毒,可减少A549肺上皮细胞烟曲霉(A. fumigatus)感染[6]。
Brilacidin tetrahydrochloride联合卡泊芬净可明显清除侵袭性肺曲霉病免疫抑制小鼠模型中的烟曲霉肺感染。真菌性角膜炎小鼠模型中,单用Brilacidin tetrahydrochloride (5 uL,2.5 mM;16times in 3days)也可减少烟曲霉的真菌感染并减缓疾病发展[7]。