Work

Novel Multifunctional Cannabidiol-Based Analogues with In Silico, In Vitro, and In Vivo Anti-SARS-CoV-2 Effect

Year: 2025

Type: article

Abstract: Background and Purpose: COVID-19 was responsible for millions of deaths worldwide. This study aimed to identify substances with in vitro and in vivo effect agains the virus. Experimental Approach: compounds PQM-243 and PQM-249, two terpene-N-acyl-aryl-hydrazone analogues were evaluated in vitro against SARS-CoV-2 to evaluate an antiviral activity and an inhibitory activity against angiotensin converting enzyme 2 (ACE2). A possible inhibitory effect inhibiting the interaction between RBD protein and/or ACE2 was evaluates using LUMMIT kit. A SARS-CoV-2-induced pulmonary pneumonia model was developed to evaluate the effects of compounds after 3 days of treatment. Key Results: PQM-243 and PQM-249 exhibited IC50 0.005 and 0.170 µM against the virus with selective index of >20,000 and 588.23 and IC50 against ACE2 was 12.1 and 13.3, respectively. All concentrations used significantly reduced interactions between ACE2 and RBD. Computational data suggest these new compounds as potent direct anti-SARS-CoV-2 agents, capable of reducing both virus viability and its invasive ability in the host cells by reducing the interaction between RBD and ACE2. It was also demonstrated that even when administered by oral route, both compounds reduced SARS-CoV-2-induced lung inflammation. Conclusion and Implications: our data suggest that compounds can act as potent direct anti-SARS-CoV-2 agents reducing both viral viability and host cell entry. Both compounds exhibited a significant multi-target-directed pharmacological profile, also reducing SARS-CoV-2-induced lung inflammation when administered orally. These findings support further investigation of PQM-243 and PQM-249 as promising prototypes for the development of innovative drug candidates targeting SARS-CoV-2 and other virus-related respiratory diseases.

Source: Pharmaceuticals

DOI: 10.3390/ph18101565