Molecular Modeling Targeting the ACE2 Receptor

Molecular Modeling Targeting the ACE2 Receptor with Cannabis sativa’s Active Ingredients for Antiviral Drug Discovery against SARS-CoV-2 Infections

The emergence of a novel coronavirus that later on rendered a global pandemic, caused desperation within the communities and drove increased interest in exploring medicinal plant–based therapeutics to treat and prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infections. Many medicinal plants have been reported to have antiviral, anti-inflammatory, and immunomodulatory effects that hinder, cure, or ease the symptoms of COVID-19 infection. This exploratory study seeks to dock the active components of Cannabis sativa, a natural plant with several pharmacological and biological properties, with the angiotensin-converting enzyme II (ACE2) receptor. A total of 3 C. sativa active components have been found to bind to the ACE2 protein active site and could inhibit spike binding, although they do not compete directly with the receptor-binding domain (RBD) of SARS-CoV-2. 6-Prenylapigenin, cannabivarin (CBN-C3), and Δ8-tetrahydrocannabinolic acid-A (Δ8-THCA) have a greater affinity (−8.3, −8.3, and −8.0 kcal/mol, respectively) and satisfactory interaction with ACE2 than its inhibitor MLN-4760 (−7.1 kcal/mol). These potential drugs with higher affinity for the ACE2 receptor and adequate absorption, distribution, metabolism, excretion, and toxicity (ADMET) values are candidates for treating or preventing SARS-CoV-2 infections. In vitro and in vivo investigations are needed to evaluate further the efficacy and toxicity of these hit compounds.