Cannabidiolic acid for COVID-19

The fast mutation of COVID-19 viruses still confuses us, and the mRNA vaccines do not inhibit the infection and may protect against the heavy disease. The infection mechanism is described with the protein-protein binding stereo structure; therefore, the infection strength of variants has been estimated from the protein-protein (S-RBD binding with ACE-2) interaction energy values calculated using a molecular mechanics program. The binding strength order was Alfa < Lambda < WT < FE.1 < XBB1.5 < EG.5 ≈ BQ.1 ≈ Alpha+E484K ≈ Omicron XBB.1.16 ≈ Epsilon, Iota < EG.5 < Delta plus ≈ Beta, Kappa B.1.621 ≈ KP.3 ≈ Kappa B.1.617.1 ≈ Delta B.1.517.2 < KP.2 < BA.2.86 ≈ JN.1 ≈ HV.1 ≈ BA.1 < BA.2. The mutation from acidic amino acid to basic amino acid strength the binding. The substitute size of amino acids causes the steric hindrance for the binding. The affinity level supports the infection strength. Various proposed infection inhibitors are quantitatively analyzed. TCA acids and natural polyphenols inhibit the binding of S-RBD to ACE-2. The cocktail dose of known medicines may enhance their performance. The inhibiting multiplication may be achieved using glycated compounds that bind glycoproteins and reduce glycoprotein activities.

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global COVID-19 pandemic, challenging healthcare systems worldwide. Effective therapeutic strategies against this novel coronavirus remain limited, underscoring the urgent need for innovative approaches. The present research investigates the potential of cannabis compounds as therapeutic agents against SARS-CoV-2 through their interaction with the virus’s papain-like protease (PLpro) protein, a crucial element in viral replication and immune evasion. Computational methods, including molecular docking and molecular dynamics (MD) simulations, were employed to screen cannabis compounds against PLpro and analyze their binding mechanisms and interaction patterns. The results showed cannabinoids with binding affinities ranging from −6.1 kcal/mol to −4.6 kcal/mol, forming interactions with PLpro. Notably, Cannabigerolic and Cannabidiolic acids exhibited strong binding contacts with critical residues in PLpro’s active region, indicating their potential as viral replication inhibitors. MD simulations revealed the dynamic behavior of cannabinoid–PLpro complexes, highlighting stable binding conformations and conformational changes over time. These findings shed light on the mechanisms underlying cannabis interaction with SARS-CoV-2 PLpro, aiding in the rational design of antiviral therapies. Future research will focus on experimental validation, optimizing binding affinity and selectivity, and preclinical assessments to develop effective treatments against COVID-19.

Since the outbreak of COVID-19, researchers have been working tirelessly to discover effective ways to combat coronavirus infection. The use of computational drug repurposing methods and molecular docking has been instrumental in identifying compounds that have the potential to disrupt the binding between the spike glycoprotein of SARS-CoV-2 and human ACE2 (hACE2). Moreover, the pseudovirus approach has emerged as a robust technique for investigating the mechanism of virus attachment to cellular receptors and for screening targeted small molecule drugs. Pseudoviruses are viral particles containing envelope proteins, which mediate the virus’s entry with the same efficiency as that of live viruses but lacking pathogenic genes. Therefore, they represent a safe alternative to screen potential drugs inhibiting viral entry, especially for highly pathogenic enveloped viruses. In this review, we have compiled a list of antiviral plant extracts and natural products that have been extensively studied against enveloped emerging and re-emerging viruses by pseudovirus technology. The review is organized into three parts: (1) construction of pseudoviruses based on different packaging systems and applications; (2) knowledge of emerging and re-emerging viruses; (3) natural products active against pseudovirus-mediated entry. One of the most crucial stages in the life cycle of a virus is its penetration into host cells. Therefore, the discovery of viral entry inhibitors represents a promising therapeutic option in fighting against emerging viruses.