Unveiling the Broad-Spectrum Efficacy of Volatile Terpenes to Fight Against SARS-COV-2-Associated Mucormycosis

Mucormycosis, a life-threatening fungal infection caused by Mucorales, affects immunocompromised patients, especially SARS-CoV-2 ones. Existing antifungal therapies, like amphotericin B, have serious health risks. The current study reviews the literature regarding an overview of SARS-CoV-2-associated mucormycosis, along with different terpenes from diverse edible sources, such as basil, ginger, and clove, which are detected till June 2024. The antifungal potential of collected terpenes, their classifications, mechanisms of action, minimum inhibitory concentration (MIC) values, and future perspectives are discussed here. The search identified 89 fungicidal volatile terpenes, belonging to about 26 families, from which 45 were selected for further in silico analysis. The results highlighted oryzalexin B (60), oryzalexin D (62), carvacrol (4), mansorin B (66), muzigadial (86), and lubimin (80) as potential antifungal agents against lanosterol 14α-demethylase, CotH3, and mucoricin as potential targets in Mucorales. CotH3 is crucial for activating GRP-78, a host co-receptor for ACE2, which is essential for SARS-CoV-2 pathogenesis. Additionally, carvacrol was in vitro investigated against Mucor racemosus via the agar diffusion method, giving an MIC value of 1 mg/mL, compared to 0.1 mg/mL of ketoconazole. This study suggests promising potential for volatile terpenes in combating SARS-CoV-2-associated mucormycosis, with the need for further refined in vitro and in vivo studies to establish clinical efficacy.