Computational analysis of compounds in the Guduchyadi Ayurvedic formulation and their potential interactions with SARS-CoV-2 Proteins

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a highly pathogenic and transmissible virus that has caused over 7 million deaths worldwide, as of early 2025, according to the World Health Organization (WHO). The very first case of Coronavirus disease (COVID-19) was reported in December 2019 in China, which was caused by SARS-CoV-2. Classical Ayurvedic texts have documented several Ayurvedic formulation for gastrointestinal disorders and fever. Some of these formulations were recommended to manage viral infections primarily affecting the respiratory system, due to pharmacological properties to address blood vitiated situations. This study aims to investigate, through in silico methods, the potential inhibitory interactions between bioactive compounds from the Ayurvedic formulation Guduchyadi and key SARS-CoV-2 proteins. Based on the Ayurvedic literature, constituents of the Guduchyadi formulation, the four medicinal plants, i.e. Tinospora cordifolia (Guduchi), Solanum xanthocarpum (Kantkari), Inula racemose (Pushkarmula) and Zingiber officinale (Sunthi), are known for broad spectrum therapeutic properties. To investigate potential interactions of the bioactive compounds from these herbal constituents with SARS-CoV-2 proteins, we gathered chemical structure information from the available published literature and carried out molecular docking experiments. These molecular docking experiments of the collected compound data were carried with the key SARS-CoV-2 proteins, including main protease (Mpro), RNA-dependeant RNA polymerase (RdRp) and spike protein. Our results have shown strong interactions between bioactive compounds from Guduchyadi with the key SARS-CoV-2 proteins. Our results have shown that Zingiber officinale (Ginger) compound: (8)-gingerol (CID: 168114) and Tinospora cordifolia (Giloy) compounds: 20-hydroxyecdysone (CID: 5459840) and Tinosporinone (CID: 42607646) have shown strong binding affinity with Mpro protein. Using the available single cell-RNA-Seq (Sc-RNA-Seq) data, we have predicted potential super-enhancers within the human genome, that could be targeted by these compounds to control the virial load. Therefore, the current study suggests a high affinity of Guduchyadi compounds with the SARS-CoV-2 proteins. Further preclinical studies, targeting the lead compounds identified in this study of the Guduchyadi formulation, could provide supporting evidence and enhance our understanding of the formulation’s mode of action and further clinical development.