Alliin for COVID-19

The global impact of the COVID-19 crisis has underscored the need for novel therapeutic candidates capable of efficiently targeting essential viral proteins. Existing therapeutic strategies continue to encounter limitations such as reduced efficacy against emerging variants, safety concerns, and suboptimal pharmacodynamics, which emphasize the potential of natural-origin compounds as supportive agents with immunomodulatory, anti-inflammatory, and antioxidant benefits. The present study significantly advances prior molecular docking research through comprehensive virtual screening of structurally related analogs derived from antiviral phytochemicals. These compounds were evaluated specifically against the SARS-CoV-2 main protease (3CLpro) and papain-like protease (PLpro). Utilizing chemical similarity algorithms via the ChEMBL database, over 600 candidate molecules were retrieved and subjected to automated docking, interaction pattern analysis, and comprehensive ADMET profiling. Several analogs showed enhanced binding scores relative to their parent scaffolds, with CHEMBL1720210 (a shogaol-derived analog) demonstrating strong interaction with PLpro (−9.34 kcal/mol), and CHEMBL1495225 (a 6-gingerol derivative) showing high affinity for 3CLpro (−8.04 kcal/mol). Molecular interaction analysis revealed that CHEMBL1720210 forms hydrogen bonds with key PLpro residues including GLY163, LEU162, GLN269, TYR265, and TYR273, complemented by hydrophobic interactions with TYR268 and PRO248. CHEMBL1495225 establishes multiple hydrogen bonds with the 3CLpro residues ASP197, ARG131, TYR239, LEU272, and GLY195, along with hydrophobic contacts with LEU287. Gene expression predictions via DIGEP-Pred indicated that the top-ranked compounds could influence biological pathways linked to inflammation and oxidative stress, processes implicated in COVID-19’s pathology. Notably, CHEMBL4069090 emerged as a lead compound with favorable drug-likeness and predicted binding to PLpro. Overall, the applied in silico framework facilitated the rational prioritization of bioactive analogs with promising pharmacological profiles, supporting their advancement toward experimental validation and therapeutic exploration against SARS-CoV-2.

Background: COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly pathogenic human coronavirus (CoV). For the treatment of COVID-19, various drugs, ayurvedic formulations, used for other diseases, were repurposed. Ayurveda and yoga exhibited a pivotal role in the treatment of COVID-19. Various medicinal plants, including garlic, tulsi, clove, cinnamon, ginger, black pepper, and turmeric, are recommended for the prevention of COVID-19 as immunity boosters along with their antiviral property Objective: In view of the drug repurposing approach, the present work has been initiated with the broader objectives of screening and identification of phytoconstituents of Indian spices against targets, namely furin, 3C-like protease (3CL-PRO), NSP-9 RNA binding protein, papain-like protease, RNA dependent RNA polymerase (RDRP), spike protein concerned with life cycle of SARS-CoV-2 using in-silico tools. Method: The phytoconstituents of Indian spices were screened for interaction with several targets using a molecular docking approach with the help of Discovery Studio 4.5 software. Furthermore, the pharmacokinetic analyses of selected ligands using ADMET and Lipinski’s rule of five were also performed. Result: In the present study, more than 35 active phytoconstituents of Indian spices were screened for interaction with several identified targets of Covid-19 using a molecular docking approach. The ligands, namely morin, gingerol, myristic acid, quercetin, gallic acid, octacosanal, and alliin were found to be the top interacting ligands with the targets analyzed. Conclusion: Based on the present in-silico finding, the active components of spices could be considered for drug-lead compounds against COVID-19.